Skip to main content Accessibility help
×
Hostname: page-component-8448b6f56d-sxzjt Total loading time: 0 Render date: 2024-04-18T02:18:24.362Z Has data issue: false hasContentIssue false

58 - Mechanisms of pituitary tumorigenesis

from Part 3.2 - Molecular pathology: cancers of the nervous system

Published online by Cambridge University Press:  05 February 2015

Shereen Ezzat
Affiliation:
Department of Medicine, University of Toronto and the Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada
Sylvia L. Asa
Affiliation:
Department of Pathology and Laboratory Medicine, University of Toronto, Department of Pathology, University Health Network, Toronto, Ontario, Canada
Edward P. Gelmann
Affiliation:
Columbia University, New York
Charles L. Sawyers
Affiliation:
Memorial Sloan-Kettering Cancer Center, New York
Frank J. Rauscher, III
Affiliation:
The Wistar Institute Cancer Centre, Philadelphia
Get access

Summary

Introduction

The pituitary, a small bean-shaped gland at the base of the brain, maintains multiple homeostatic functions, including metabolism, growth, and reproduction. Most pituitary tumors are adenomas that develop in the adenohypophysis, the epithelial anterior lobe composed of six cell types that secrete polypeptide hormones.

Pituitary adenomas exhibit a wide range of hormonal and proliferative behaviors (1). They may be small, slowly growing and hormonally inactive, detected as radiographic “incidentalomas” or at post-mortem examination. When they produce hormones in excess, they cause mood disorders, sexual dysfunction, infertility, obesity and disfigurement, hypertension, diabetes mellitus, and accelerated heart disease. Untreated, hormone excess syndromes can be associated with diminished survival.

Some pituitary adenomas grow rapidly, producing symptoms of an intra-cranial mass, loss of normal anterior pituitary hormone production, and visual ield disturbances due to stretching of the overlying optic chiasm.hey can invade downward into paranasal sinuses, laterally into the cavernous sinuses (thereby disrupting co-ordinated eye movement) and upwards into the brain.hey can cause death by invasion of brain.

Early studies using X-chromosome inactivation proved that these adenomas are monoclonal neoplasms (2–5). Polyclonal results were attributed to contamination by normal tissue; the small adenomas associated with Cushing’s syndrome are particularly subject to this phenomenon (4,5).

Type
Chapter
Information
Molecular Oncology
Causes of Cancer and Targets for Treatment
, pp. 652 - 668
Publisher: Cambridge University Press
Print publication year: 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Asa, SL. Tumors of the pituitary gland. Atlas of Tumor Pathology, Third Series, Fascicle 22. Washington, DC:Armed Forces Institute of Pathology; 1998.
Alexander, JM, Biller, BMK, Bikkal, H, et al. Clinically nonfunctioning pituitary tumors are monoclonal in origin. Journal of Clinical Investigation 1990;86:336–40.CrossRefGoogle ScholarPubMed
Herman, V, Fagin, J, Gonsky, R, Kovacs, K, Melmed, S.Clonal origin of pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1990;71:1427–33.CrossRefGoogle ScholarPubMed
Schulte, HM, Oldfield, EH, Allolio, B, et al. Clonal composition of pituitary adenomas in patients with Cushing's disease: determination by X-chromosome inactivation analysis. Journal of Clinical Endocrinology and Metabolism 1991;73:1302–8.CrossRefGoogle ScholarPubMed
Gicquel, C, LeBouc, Y, Luton, J-P, Girad, F, Bertagna, X.Monoclonality of corticotroph macroadenomas in Cushing's disease. Journal of Clinical Endocrinology and Metabolism 1992;75:472–5.Google ScholarPubMed
Ezzat, S, Asa, SL, Couldwell, WT, et al. The prevalence of pituitary adenomas:a systematic review. Cancer 2004;101:613–19.CrossRef
Fernandez, A, Karavitaki, N, Wass, JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clinical Endocrinology (Oxford) 2010;72:377–82.CrossRefGoogle Scholar
Kane, LA, Leinung, MC, Scheithauer, BW, et al. Pituitary adenomas in childhood and adolescence. Journal of Clinical Endocrinology and Metabolism 1994;79:1135–40.Google ScholarPubMed
Kovacs, K, Ryan, N, Horvath, E, Singer, W, Ezrin, C.Pituitary adenomas in old age. Journal of Gerontology 1980;35:16–22.CrossRefGoogle ScholarPubMed
Kovacs, K, Horvath, E. Tumors of the pituitary gland. Atlas of Tumor Pathology, Second Series, Fascicle 21. Washington, DC: Armed Forces Institute of Pathology, 1986.
Asa, SL, Puy, LA, Lew, AM, Sundmark, VC, Elsholtz, HP.Cell type-specific expression of the pituitary transcription activator Pit-1 in the human pituitary and pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1993;77:1275–80.Google ScholarPubMed
Friend, KE, Chiou, Y-K, Laws, ER, Jr., Lopes, MBS, Shupnik MA. Pit-1 messenger ribonucleic acid is differentially expressed in human pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1993;77:1281–6.Google ScholarPubMed
Zafar, M, Ezzat, S, Ramyar, L, et al. Cell-specific expression of estrogen receptor in the human pituitary and its adenomas. Journal of Clinical Endocrinology and Metabolism 1995;80:3621–7.Google ScholarPubMed
Friend, KE, Chiou, YK, Lopes, MBS, et al. Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas. Journal of Clinical Endocrinology and Metabolism 1994;78:1497–504.Google ScholarPubMed
Lamolet, B, Pulichino, AM, Lamonerie, T, et al. A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins. Cell 2001;104:849–59.CrossRef
Asa, SL, Bamberger, A-M, Cao, B, et al. The transcription activator steroidogenic factor-1 is preferentially expressed in the human pituitary gonadotroph. Journal of Clinical Endocrinology and Metabolism 1996;81:2165–70.Google ScholarPubMed
Castrillo, J-L, Theill, LE, Karin, M. Function of the homeodomain protein GHF1 in pituitary cell proliferation. Science 1991;253:197–9.CrossRef
DeLellis, RA, Lloyd, RV, Heitz, PU, Eng, C. Pathology and genetics of tumours of endocrine organs. WHO Classification of Tumours. Lyons, France: IARC Press; 2004.
Thapar, K, Kovacs, K, Scheithauer, BW, et al. Proliferative activity and invasiveness among pituitary adenomas and carcinomas:an analysis using the MIB-1 antibody. Neurosurgery 1996;38:99–107.CrossRef
Chandrasekharappa, SC, Guru, SC, Manickam, P, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 1997;276:404–7.CrossRef
Zhuang, Z, Ezzat, S, Vortmeyer, AO, et al. Mutations of the MEN1 tumor suppressor gene in pituitary tumors. Cancer Research 1997;57:5446–51.
Asa, SL, Somers, K, Ezzat, S.The MEN-1 gene is rarely down-regulated in pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1998;83:3210–12.Google ScholarPubMed
Kirschner, LS, Carney, JA, Pack, SD, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nature Genetics 2000;26:89–92.CrossRef
Yin, Z, Williams-Simons, L, Parlow, AF, Asa, S, Kirschner, LS. Pituitary-specific knockout of the carney complex gene prkar1a leads to pituitary tumorigenesis. Molecular Endocrinology 2008;22:380–7.CrossRef
Vierimaa, O, Georgitsi, M, Lehtonen, R, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 2006;312:1228–30.CrossRef
Kuzhandaivelu, N, Cong, YS, Inouye, C, Yang, WM, Seto, E. XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation. Nucleic Acids Research 1996;24:4741–50.CrossRef
Carlson, DB, Perdew, GH.A dynamic role for the Ah receptor in cell signaling? Insights from a diverse group of Ah receptor interacting proteins. Journal of Biochemical and Molecular Toxicology 2002;16:317–25.CrossRefGoogle Scholar
Kashuba, EV, Gradin, K, Isaguliants, M, et al. Regulation of transactivation function of the aryl hydrocarbon receptor by the Epstein-Barr virus-encoded EBNA-3 protein. Journal of Biological Chemistry 2006;281:1215–23.CrossRefGoogle ScholarPubMed
Trivellin, G, Butz, H, Delhove, J, et al. MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro. American Journal of Physiology, Endocrinology and Metabolism 2012;303:E708–19.
Ezzat, S, Asa, SL. Mechanisms of disease: the pathogenesis of pituitary tumors. Nature Clinical Practice Endocrinology and Metabolism 2006;2:220–30.CrossRef
Jacks, T, Fazeli, A, Schmitt, EM, et al. Effects of an Rb mutation in the mouse. Nature 1992;359:295–300.CrossRef
Cryns, VL, Alexander, JM, Klibanski, A, Arnold, A.The retinoblastoma gene in human pituitary tumors. Journal of Clinical Endocrinology and Metabolism 1993;77:644–6.Google ScholarPubMed
Pei, L, Melmed, S, Scheithauer, B, et al. Frequent loss of heterozygosity at the retinoblastoma susceptibility gene (RB) locus in aggressive pituitary tumors: evidence for a chromosome 13 tumor suppressor gene other than RB. Cancer Research 1995;55:1613–16.
Woloschak, M, Yu, A, Xiao, J, Post, KD. Abundance and state of phosphorylation of the retinoblastoma gene product in human pituitary tumors. International Journal of Cancer 1996;67:16–19.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Bates, AS, Farrell, WE, Bicknell, EJ, et al. Allelic deletion in pituitary adenomas reflects aggressive biological activity and has potential value as a prognostic marker. Journal of Clinical Endocrinology and Metabolism 1997;82:818–24.Google ScholarPubMed
Tsai, KY, MacPherson, D, Rubinson, DA, et al. ARF mutation accelerates pituitary tumor development in Rb+/– mice. Proceedings of the National Academy of Sciences USA 2002;99:16 865–70.
Lasorella, A, Rothschild, G, Yokota, Y, Russell, RG, Iavarone, A. Id2 mediates tumor initiation, proliferation, and angiogenesis in Rb mutant mice. Molecular and Cellular Biology 2005;25:3563–74.CrossRef
Buckley, N, Bates, AS, Broome, JC, et al. p53 protein accumulation in Cushings adenomas and invasive non-functional adenomas. Journal of Clinical Endocrinology and Metabolism 1994;79:1513–16.Google ScholarPubMed
Sumi, T, Stefaneanu, L, Kovacs, K, Asa, SL, Rindi, G. Immunohistochemical study of p53 protein in human and animal pituitary tumors. Endocrine Pathology 1993;4:95–9.CrossRef
Thapar, K, Scheithauer, BW, Kovacs, K, Pernicone, PJ, Laws, ER p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 1996;38:765–71.CrossRef
Levy, A, Hall, L, Yeundall, WA, Lightman, SL. p53 gene mutations in pituitary adenomas:rare events. Clinical Endocrinology (Oxford) 1994;41:809–14.CrossRef
Amar, AP, Hinton, DR, Krieger, MD, Weiss, MH. Invasive pituitary adenomas:significance of proliferation parameters. Pituitary 1999;2:117–22.CrossRef
Sherr, CJ, Roberts, JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes and Development 1995;9:1149–63.CrossRef
Woloschak, M, Yu, A, Post, KD. Frequent inactivation of the p16 gene in human pituitary tumors by gene methylation. Molecular Carcinogenesis 1997;19:221–4.3.0.CO;2-F>CrossRef
Frost, SJ, Simpson, DJ, Clayton, RN, Farrell, WE. Transfection of an inducible p16/CDKN2A construct mediates reversible growth inhibition and G1 arrest in the AtT20 pituitary tumor cell line. Molecular Endocrinology 1999;13:1801–10.CrossRef
Lloyd, RV, Jin, L, Qian, X, Kulig, E.Aberrant p27kip1 expression in endocrine and other tumors. American Journal of Pathology 1997;150:401–7.Google ScholarPubMed
Nakayama, K, Ishida, N, Shirane, M, et al. Mice lacking p27Kip1 display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 1996;85:707–20.CrossRef
Kiyokawa, H, Kineman, RD, Manova-Todorova, KO, et al. Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kip1. Cell 1996;85:721–32.CrossRef
Fero, ML, Rivkin, M, Tasch, M, et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27Kip1-deficient mice. Cell 1996;85:733–44.CrossRef
Bamberger, CM, Fehn, M, Bamberger, AM, et al. Reduced expression levels of the cell-cycle inhibitor p27Kip1 in human pituitary adenomas. European Journal of Endocrinology 1999;140:250–5.CrossRefGoogle ScholarPubMed
Dahia, PL, Aguiar, RC, Honegger, J, et al. Mutation and expression analysis of the p27/kip1 gene in corticotrophin- secreting tumours. Oncogene 1998;16:69–76.CrossRef
Liu, W, Asa, SL, Ezzat, S. Vitamin D and its analog EB1089 induce p27 accumulation and diminish association of p27 with Skp2 independent of PTEN in pituitary corticotroph cells. Brain Pathology 2002;12:412–19.CrossRef
Tong, W, Pollard, JW. Genetic evidence for the interactions of cyclin D1 and p27(Kip1) in mice. Molecular and Cellular Biology 2001;21:1319–28.CrossRef
Franklin, DS, Godfrey, VL, Lee, H, et al. CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis. Genes and Development 1998;12:2899–911.CrossRef
Zhang, X, Sun, H, Danila, DC, et al. Loss of expression of GADD45 gamma, a growth inhibitory gene, in human pituitary adenomas:implications for tumorigenesis. Journal of Clinical Endocrinology and Metabolism 2002;87:1262–7.Google ScholarPubMed
Bahar, A, Bicknell, JE, Simpson, DJ, Clayton, RN, Farrell, WE. Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary adenomas, is associated with CpG island methylation. Oncogene 2004;23:936–44.CrossRef
Zhao, J, Dahle, D, Zhou, Y, Zhang, X, Klibanski, A.Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. Journal of Clinical Endocrinology and Metabolism 2005;90:2179–86.CrossRefGoogle ScholarPubMed
Bahar, A, Simpson, DJ, Cutty, SJ, et al. Isolation and characterization of a novel pituitary tumor apoptosis gene. Molecular Endocrinology 2004;18:1827–39.CrossRef
Karga, HJ, Alexander, JM, Hedley-Whyte, ET, Klibanski, A, Jameson, JL. Ras mutations in human pituitary tumors. Journal of Clinical Endocrinology and Metabolism 1992;74:914–19.CrossRef
Cai, WY, Alexander, JM, Hedley-Whyte, ET, et al. Ras mutations in human prolactinomas and pituitary carcinomas. Journal of Clinical Endocrinology and Metabolism 1994;78:89–93.
Zou, H, McGarry, TJ, Bernal, T, Kirschner, MW. Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 1999;285:418–22.CrossRef
Pei, L, Melmed, S. Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Molecular Endocrinology 1997;11:433–41.CrossRef
Ramos-Morales, F, Dominguez, A, Romero, F, et al. Cell cycle regulated expression and phosphorylation of hpttg proto- oncogene product. Oncogene 2000;19:403–9.CrossRef
Chesnokova, V, Kovacs, K, Castro, AV, Zonis, S, Melmed, S. Pituitary hypoplasia in Pttg–/– mice is protective for Rb+/– pituitary tumorigenesis. Molecular Endocrinology 2005;19:2371–9.CrossRef
Martin, A, Odajima, J, Hunt, SL, et al. Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1). Cancer Cell 2005;7:591–8.CrossRef
Asa, SL, Kovacs, K. Functional morphology of the human fetal pituitary. Pathology Annual 1984;19:275–315.
Asa, SL, Kovacs, K, Laszlo, FA, Domokos, I, Ezrin, C. Human fetal adenohypophysis. Histologic and immunocytochemical analysis. Neuroendocrinology 1986;43:308–16.
Asa, SL. The role of hypothalamic hormones in the pathogenesis of pituitary adenomas. Pathology Research and Practice 1991;187:581–3.CrossRef
Kovacs, K, Horvath, E, Rewcastle, NB, Ezrin, C. Gonadotroph cell adenoma of the pituitary in a woman with long-standing hypogonadism. Archives of Gynecology 1980;229:57–65.CrossRef
Lloyd, RV.Estrogen-induced hyperplasia and neoplasia in the rat anterior pituitary gland: an immunohistochemical study. American Journal of Pathology 1983;113:198–206.Google Scholar
Scheithauer, BW, Kovacs, K, Randall, RV. The pituitary gland in untreated Addison's disease: a histologic and immunocytologic study of 18 adenohypophyses. Archives of Pathology and Laboratory Medicine 1983;107:484–7.
Khalil, A, Kovacs, K, Sima, AAF, Burrow, GN, Horvath, E.Pituitary thyrotroph hyperplasia mimicking prolactin-secreting adenoma. Journal of Endocrinological Investigation 1984;7:399–404.CrossRefGoogle ScholarPubMed
Scheithauer, BW, Kovacs, K, Randall, RV, Ryan, N. Pituitary gland in hypothyroidism. Histologic and immunocytologic study. Archives of Pathology and Laboratory Medicine 1985;109:499–504.
Horvath, E. Pituitary hyperplasia. Pathology Research and Practice 1988;183:623–5.CrossRef
Nicolis, G, Shimshi, M, Allen, C, Halmi, NS, Kourides, IA.Gonadotropin-producing pituitary adenoma in a man with long-standing primary hypogonadism. Journal of Clinical Endocrinology and Metabolism 1988;66:237–41.CrossRefGoogle Scholar
Atchison, JA, Lee, PA, Albright, AL.Reversible suprasellar pituitary mass secondary to hypothyroidism. Journal of the American Medical Association 1989;262:3175–7.CrossRefGoogle ScholarPubMed
Horvath, E, Lloyd, RV, Kovacs, K. Propylthiouracyl-induced hypothyroidism results in reversible transdifferentiation of somatotrophs into thyroidectomy cells: a morphologic study of the rat pituitary including immunoelectron microscopy. Laboratory Investigation 1990;63:511–20.
Vidal, S, Horvath, E, Kovacs, K, et al. Transdifferentiation of somatotrophs to thyrotrophs in the pituitary of patients with protracted primary hypothyroidism. Virchows Archiv 2000;436:43–51.CrossRef
Ezzat, S, Asa, SL, Stefaneanu, L, et al. Somatotroph hyperplasia without pituitary adenoma associated with a long standing growth hormone-releasing hormone-producing bronchial carcinoid. Journal of Clinical Endocrinology and Metabolism 1994;78:555–60.Google ScholarPubMed
Billestrup, N, Swanson, LW, Vale, W. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro. Proceedings of the National Academy of Sciences USA 1986;83:6854–7.CrossRef
Godfrey, P, Rahal, J, Beamer, W, et al. GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nature Genetics 1993;4:227–32.CrossRef
Stefaneanu, L, Kovacs, K, Horvath, E, et al. Adenohypophysial changes in mice transgenic for human growth hormone-releasing factor:a histological, immunocytochemical, and electron microscopic investigation. Endocrinology 1989;125:2710–18.CrossRef
Thorner, MO, Perryman, RL, Cronin, MJ, et al. Somatotroph hyperplasia:Successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth hormone-releasing factor. Journal of Clinical Investigation 1982;70:965–77.CrossRefGoogle ScholarPubMed
Sano, T, Asa, SL, Kovacs, K. Growth hormone-releasing hormone-producing tumors:clinical, biochemical, and morphological manifestations. Endocrine Reviews 1988;9:357–73.CrossRef
Levy, A, Lightman, SL.Growth hormone-releasing hormone transcripts in human pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1992;74:1474–6.Google ScholarPubMed
Joubert (Bression), D, Benlot, C, Lagoguey, A, et al. Normal and growth hormone (GH)-secreting adenomatous human pituitaries release somatostatin and GH-releasing hormone. Journal of Clinical Endocrinology and Metabolism 1989;68:572–7.CrossRefGoogle Scholar
Thapar, K, Kovacs, K, Stefaneanu, L, et al. Overexpression of the growth-hormone-releasing hormone gene in acromegaly-associated pituitary tumors: an event associated with neoplastic progression and aggressive behavior. American Journal of Pathology 1997;151:769–84.Google ScholarPubMed
Kawakita, S, Asa, SL, Kovacs, K. Effects of growth hormone-releasing hormone (GHRH) on densely granulated somatotroph adenomas and sparsely granulated somatotroph adenomas in vitro: a morphological and functional investigation. Journal of Endocrinological Investigation 1989;12:443–8.CrossRef
Spada, A, Elahi, FR, Arosio, M, et al. Lack of desensitization of adenomatous somatotrophs to growth hormone-yreleasing hormone in acromegaly. Journal of Clinical Endocrinology and Metabolism 1987;64:585–91.CrossRefGoogle ScholarPubMed
Asa, SL, Kovacs, K, Stefaneanu, L, et al. Pituitary adenomas in mice transgenic for growth hormone-releasing hormone. Endocrinology 1992;131:2083–9.CrossRef
Lee, EJ, Kotlar, TJ, Ciric, I, et al. Absence of constitutively activating mutations in the GHRH receptor in GH-producing pituitary tumors. Journal of Clinical Endocrinology and Metabolism 2001;86:3989–95.CrossRefGoogle ScholarPubMed
Hashimoto, K, Koga, M, Motomura, T, et al. Identification of alternatively spliced messenger ribonucleic acid encoding truncated growth hormone-releasing hormone receptor in human pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1995;80:2933–9.Google ScholarPubMed
Gilman AG. G proteins: transducers of receptor-generated signals. Annual Review of Biochemistry 1987;56:615–49.CrossRef
Vallar, L, Spada, A, Giannattasio, G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature 1987;330:566–8.CrossRef
Lyons, J, Landis, CA, Harsh, G, et al. Two G protein oncogenes in human endocrine tumors. Science 1990;249:655–9.CrossRef
Hayward, BE, Barlier, A, Korbonits, M, et al. Imprinting of the G(s)alpha gene GNAS1 in the pathogenesis of acromegaly. Journal of Clinical Investigation 2001;107:R31–6.CrossRefGoogle Scholar
Landis, CA, Harsh, G, Lyons, J, et al. Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein. Journal of Clinical Endocrinology and Metabolism 1990;71:1416–20.CrossRefGoogle ScholarPubMed
Spada, A, Arosio, M, Bochicchio, D, et al. Clinical, biochemical and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. Journal of Clinical Endocrinology and Metabolism 1990;71:1421–6.CrossRefGoogle ScholarPubMed
Bertherat, J, Chanson, P, Montminy, M. The cyclic adenosine 3ʹ5ʹ-monophosphate-responsive factor CREB is constitutively activated in human somatotroph adenomas. Molecular Endocrinology 1995;9:777–83.
Harris, PE, Alexander, JM, Bikkal, HA, et al. Glycoprotein hormone α-subunit production in somatotroph adenomas with and without Gsα mutations. Journal of Clinical Endocrinology and Metabolism 1992;75:918–23.Google Scholar
Ezzat, S, Kontogeorgos, G, Redelmeier, DA, et al. In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide. European Journal of Endocrinology 1995;133:686–90.CrossRefGoogle ScholarPubMed
Bhayana, S, Booth, GL, Asa, SL, Kovacs, K, Ezzat, S.The implication of somatotroph adenoma phenotype to somatostatin analog responsiveness in acromegaly. Journal of Clinical Endocrinology and Metabolism 2005;90:6290–5.CrossRefGoogle ScholarPubMed
Oyesiku, NM, Evans, C-O, Brown, MR, et al. Pituitary adenomas:Screening for Gαq mutations. Journal of Clinical Endocrinology and Metabolism 1997;82:4184–8.Google Scholar
Williamson, EA, Daniels, M, Foster, S, et al. Gsα and Gi2α mutations in clinically non-functioning pituitary tumours. Clinical Endocrinology (Oxford) 1994;41:815–20.CrossRef
Kelijman, M, Williams, TC, Downs, TR, Frohman, LA. Comparison of the sensitivity of growth hormone secretion to somatostatin in vivo and in vitro in acromegaly. Journal of Clinical Endocrinology and Metabolism 1988;67:958–63.CrossRef
Reubi, JC, Landolt, AM. The growth hormone responses to octreotide in acromegaly correlate with adenoma somatostatin receptor status. Journal of Clinical Endocrinology and Metabolism 1989;68:844–50.CrossRefGoogle ScholarPubMed
Bertherat, J, Chanson, P, Dewailly, D, et al. Somatostatin receptors, adenylate cyclase activity, and growth hormone (GH) response to octreotide in GH-secreting adenomas. Journal of Clinical Endocrinology and Metabolism 1993;77:1577–83.Google ScholarPubMed
Miller, GM, Alexander, JM, Bikkal, HA, et al. Somatostatin receptor subtype gene expression in pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1995;80:1386–92.Google ScholarPubMed
Danila, DC, Haidar, JN, Zhang, X, et al. Somatostatin receptor-specific analogs:effects on cell proliferation and growth hormone secretion in human somatotroph tumors. Journal of Clinical Endocrinology and Metabolism 2001;86:2976–81.Google ScholarPubMed
Ballare, E, Persani, L, Lania, AG, et al. Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatment. Journal of Clinical Endocrinology and Metabolism 2001;86:3809–14.CrossRefGoogle Scholar
Peillon, F, Liappi, G, Garnier, P, et al. In vitro secretion of somatostatin (SRIH) by human adenomatous somatotropic cells: relation with somatotropic hormone (GH) release and modulation by thyroliberin (TRH) [Fre]. Comptes Rendus de l’Academy des Sciences [III] 1988;306:161–6.
Levy, L, Bourdais, J, Mouhieddine, B, et al. Presence and characterization of the somatostatin precursor in normal human pituitaries and in growth hormone secreting adenomas. Journal of Clinical Endocrinology and Metabolism 1993;76:85–90.Google ScholarPubMed
Filopanti, M, Ballare, E, Lania, AG, et al. Loss of heterozygosity at the SS receptor type 5 locus in human GH- and TSH-secreting pituitary adenomas. Journal of Endocrinological Investigation 2004;27:937–42.CrossRefGoogle Scholar
Kola, B, Korbonits, M, Diaz-Cano, S, et al. Reduced expression of the growth hormone and type 1 insulin-like growth factor receptors in human somatotroph tumours and an analysis of possible mutations of the growth hormone receptor. Clinical Endocrinology (Oxford) 2003;59:328–38.CrossRef
Asa, SL, Coschigano, KT, Bellush, L, Kopchick, JJ, Ezzat, S.Evidence for growth hormone (GH) autoregulation in pituitary somatotrophs in GH antagonist-transgenic mice and GH receptor-deficient mice. American Journal of Pathology 2000;156:1009–15.CrossRefGoogle ScholarPubMed
Asa, SL, DiGiovanni, R, Jiang, J, et al. A growth hormone receptor mutation impairs growth hormone autofeedback signaling in pituitary tumors. Cancer Research 2007;67:7505–11.CrossRef
Yamada, M, Monden, T, Satoh, T, et al. Pituitary adenomas of patients with acromegaly express thyrotropin-releasing hormone receptor messenger RNA cloning and functional expression of the human thyrotropin-releasing hormone receptor gene. Biochemical and Biophysical Research Communications 1993;195:737–45.CrossRef
Yamada, M, Hashimoto, K, Satoh, T, et al. A novel transcript for the thyrotropin-releasing hormone receptor in human pituitary and pituitary tumors. Journal of Clinical Endocrinology and Metabolism 1997;82:4224–8.CrossRefGoogle ScholarPubMed
Gittoes, NJL, McCabe, CJ, Verhaeg, J, Sheppard, MC, Franklyn, JA.Thyroid hormone and estrogen receptor expression in normal pituitary and nonfunctioning tumors of the anterior pituitary. Journal of Clinical Endocrinology and Metabolism 1997;82:1960–7.Google ScholarPubMed
Ando, S, Sarlis, NJ, Krishnan, J, et al. Aberrant alternative splicing of thyroid hormone receptor in a TSH- secreting pituitary tumor is a mechanism for hormone resistance. Molecular Endocrinology 2001;15:1529–38.CrossRef
Abel, ED, Boers, ME, Pazos-Moura, C, et al. Divergent roles for thyroid hormone receptor beta isoforms in the endocrine axis and auditory system. Journal of Clinical Investigation 1999;104:291–300.CrossRefGoogle ScholarPubMed
Brinkmeier, ML, Stahl, JH, Gordon, DF, et al. Thyroid hormone-responsive pituitary hyperplasia independent of somatostatin receptor 2. Molecular Endocrinology 2001;15:2129–36.CrossRef
Lohrer, P, Gloddek, J, Hopfner, U, et al. Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro. Neuroendocrinology 2001;74:95–105.CrossRef
Heaney, AP, Fernando, M, Melmed, S.Functional role of estrogen in pituitary tumor pathogenesis. Journal of Clinical Investigation 2002;109:277–83.CrossRefGoogle ScholarPubMed
Shen, ES, Hardenburg, JL, Meade, EH, et al. Estradiol induces galanin gene expression in the pituitary of the mouse in an estrogen receptor alpha-dependent manner. Endocrinology 1999;140:2628–31.CrossRef
Lee, EJ, Jakacka, M, Duan, WR, et al. Adenovirus-directed expression of dominant negative estrogen receptor induces apoptosis in breast cancer cells and regression of tumors in nude mice. Molecular Medicine 2001;7:773–82.
Asa, SL, Penz, G, Kovacs, K, Ezrin, C. Prolactin cells in the human pituitary. A quantitative immunocytochemical analysis. Archives of Pathology and Laboratory Medicine 1982;106:360–3.
Scheithauer, BW, Sano, T, Kovacs, KT, et al. The pituitary gland in pregnancy: A clinicopathologic and immunohisto-chemical study of 69 cases. Mayo Clinic Proceedings 1990;65:461–74.CrossRef
Molitch, ME. Pituitary tumors and pregnancy. Growth Hormone and IGF Research 2003;13:S38–44.
Kovacs, K, Stefaneanu, L, Ezzat, S, Smyth, HS. Prolactin-producing pituitary adenoma in a male-to-female transsexual patient with protracted estrogen administration: a morphologic study. Archives of Pathology and Laboratory Medicine 1994;118:562–5.
Testa, G, Vegetti, W, Motta, T, et al. Two-year treatment with oral contraceptives in hyperprolactinemic patients. Contraception 1998;58:69–73.CrossRef
Schechter, J, Goldsmith, P, Wilson, C, Weiner, R.Morphological evidence for the presence of arteries in human prolactinomas. Journal of Clinical Endocrinology and Metabolism 1988;67:713–19.CrossRefGoogle ScholarPubMed
Wood, DF, Johnston, JM, Johnston, DG. Dopamine, the dopamine D2 receptor and pituitary tumours. Clinical Endocrinology (Oxford) 1991;35:455–66.CrossRef
Kelly, MA, Rubinstein, M, Asa, SL, et al. Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice. Neuron 1997;19:103–13.CrossRef
Asa, SL, Kelly, MA, Grandy, DK, Low, MJ. Pituitary lactotroph adenomas develop after prolonged lactotroph hyperplasia in dopamine D2 receptor-deficient mice. Endocrinology 1999;140:5348–55.CrossRef
Fiorentini, C, Guerra, N, Facchetti, M, et al. Nerve growth factor regulates dopamine D(2) receptor expression in prolactinoma cell lines via p75(NGFR)-mediated activation of nuclear factor-kappaB. Molecular Endocrinology 2002;16:353–66.
Devost, D, Boutin, JM. Autoregulation of the rat prolactin gene in lactotrophs. Molecular and Cellular Endocrinology 1999;158:99–109.CrossRef
Kelly, PA, Binart, N, Lucas, B, Bouchard, B, Goffin, V. Implications of multiple phenotypes observed in prolactin receptor knockout mice. Frontiers in Neuroendocrinology 2001;22:140–5.CrossRef
Schuff, KG, Hentges, ST, Kelly, MA, et al. Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. Journal of Clinical Investigation 2002;110:973–81.CrossRefGoogle ScholarPubMed
Jin, L, Qian, X, Kulig, E, et al. Prolactin receptor messenger ribonucleic acid in normal and neoplastic human pituitary tissues. Journal of Clinical Endocrinology and Metabolism 1997;82:963–8.Google ScholarPubMed
Carey, RM, Varma, SK, Drake, CR, Jr., et al. Ectopic secretion of corticotropin-releasing factor as a cause of Cushing's syndrome. A clinical, morphologic, and biochemical study. New England Journal of Medicine 1984;311:13–20.CrossRefGoogle ScholarPubMed
Asa, SL, Kovacs, K, Hammer, GD, et al. Pituitary corticotroph hyperplasia in rats implanted with a medullary thyroid carcinoma cell line transfected with a corticotropin-releasing hormone complementary deoxyribonucleic acid expression vector. Endocrinology 1992;131:715–20.
Asa, SL, Kovacs, K, Vale, W, Petrusz, P, Vecsei, P.Immunohistologic localization of corticotrophin-releasing hormone in human tumors. American Journal of Clinical Pathology 1987;87:327–33.CrossRefGoogle ScholarPubMed
Stenzel-Poore, MP, Cameron, VA, Vaughan, J, Sawchenko, PE, Vale, W. Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice. Endocrinology 1992;130:3378–86.CrossRef
Bamberger, CM, Schulte, HM, Chrousos, GP. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocrine Reviews 1996;17:245–61.CrossRef
Hurley, DM, Accili, D, Stratakis, CA, et al. Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. Journal of Clinical Investigation 1991;87:680–6.CrossRefGoogle ScholarPubMed
Karl, M, Lamberts, SWJ, Koper, JW, et al. Cushing's disease preceded by generalized glucocorticoid resistance: clinical consequences of a novel dominant-negative glucocorticoid receptor mutation. Proceedings of the Association of American Physicians 1996;108:296–307.
Karl, M, von Wichert, G, Kempter, E, et al. Nelson's syndrome associated with a somatic frame shift mutation in the glucocorticoid receptor gene. Journal of Clinical Endocrinology and Metabolism 1996;81:124–9.Google ScholarPubMed
Ray, DW, Littlewood, AC, Clark, AJ, Davis, JRE, White, A.Human small cell lung cancer cell lines expressing the proopiomelanocortin gene have aberrant glucocorticoid receptor function. Journal of Clinical Investigation 1994;93:1625–30.CrossRefGoogle ScholarPubMed
Ezzat, S. The role of hormones, growth factors and their receptors in pituitary tumorigenesis. Brain Pathology 2001;11:356–70.CrossRef
Ezzat, S, Walpola, IA, Ramyar, L, Smyth, HS, Asa, SL.Membrane-anchored expression of transforming growth factor-α in human pituitary adenoma cells. Journal of Clinical Endocrinology and Metabolism 1995;80:534–9.Google ScholarPubMed
Oomizu, S, Honda, J, Takeuchi, S, et al. Transforming growth factor-alpha stimulates proliferation of mammotrophs and corticotrophs in the mouse pituitary. Journal of Endocrinology 2000;165:493–501.CrossRefGoogle ScholarPubMed
McAndrew, J, Paterson, AJ, Asa, SL, McCarthy, KJ, Kudlow, JE. Targeting of transforming growth factor-α expression to pituitary lactotrophs in transgenic mice results in selective lactotroph proliferation and adenomas. Endocrinology 1995;136:4479–88.CrossRef
LeRiche, V, Asa, SL, Ezzat, S.Epidermal growth factor and its receptor (EGF-R) in human pituitary adenomas: EGF-R correlates with tumor aggressiveness. Journal of Clinical Endocrinology and Metabolism 1996;81:656–62.Google ScholarPubMed
Childs, GV, Rougeau, D, Unabia, G. Corticotropin-releasing hormone and epidermal growth factor: mitogens for anterior pituitary corticotropes. Endocrinology 1995;136:1595–602.CrossRef
Roh, M, Paterson, AJ, Asa, SL, Chin, E, Kudlow, JE. Stage-sensitive blockade of pituitary somatomammotrope development by targeted expression of a dominant negative epidermal growth factor receptor in transgenic mice. Molecular Endocrinology 2001;15:600–13.CrossRef
Ezzat, S, Zheng, L, Smyth, HS, Asa, SL. The c-erbB-2/neu proto-oncogene in human pituitary tumours. Clinical Endocrinology (Oxford) 1997;46:599–606.CrossRef
Ying, S-Y. Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone. Endocrine Reviews 1988;9:267–93.CrossRef
Danila, DC, Inder, WJ, Zhang, X, et al. Activin effects on neoplastic proliferation of human pituitary tumors. Journal of Clinical Endocrinology and Metabolism 2000;85:1009–15.Google ScholarPubMed
Haddad, G, Penabad, JL, Bashey, HM, et al. Expression of activin/inhibin subunit messenger ribonucleic acids by gonadotroph adenomas. Journal of Clinical Endocrinology and Metabolism 1994;79:1399–403.Google ScholarPubMed
Penabad, JL, Bashey, HM, Asa, SL, et al. Decreased follistatin gene expression in gonadotroph adenomas. Journal of Clinical Endocrinology and Metabolism 1996;81:3397–403.Google ScholarPubMed
Zhou, Y, Sun, H, Danila, DC, et al. Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling. Molecular Endocrinology 2000;14:2066–75.CrossRef
Mason, IJ. The ins and outs of fibroblast growth factors. Cell 1994;78:547–52.CrossRef
Gospodarowicz, D, Ferrara, N, Schweigerer, L, Neufeld, G. Structural characterization and biological functions of fibroblast growth factor. Endocrine Reviews 1987;8:95–114.CrossRef
Ferrara, N, Schweigerer, L, Neufeld, G, Mitchell, R, Gospodarowicz, D. Pituitary follicular cells produce basic fibroblast growth factor. Proceedings of the National Academy of Sciences USA 1987;84:5773–7.CrossRef
Scully, KM, Rosenfeld, MG. Pituitary development:regulatory codes in mammalian organogenesis. Science 2002;295:2231–5.CrossRef
Celli, G, LaRochelle, WJ, Mackem, S, Sharp, R, Merlino, G. Soluble dominant-negative receptor uncovers essential roles for fibroblast growth factors in multi-organ induction and patterning. EMBO Journal 1998;17:1642–55.CrossRef
Ezzat, S, Smyth, HS, Ramyar, L, Asa, SL. Heterogeneous in vivo and in vitro expression of basic fibroblast growth factor by human pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1995;80:878–84.
Li, Y, Koga, M, Kasayama, S, et al. Identification and characterization of high molecular weight forms of basic fibroblast growth factor in human pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1992;75:1436–41.Google ScholarPubMed
Zimering, MB, Katsumata, N, Sato, Y, et al. Increased basic fibroblast growth factor in plasma from multiple endocrine neoplasia type 1: relation to pituitary tumor. Journal of Clinical Endocrinology and Metabolism 1993;76:1182–7.Google ScholarPubMed
Asa, SL, Ramyar, L, Murphy, PR, Li, AW, Ezzat, S. The endogenous fibroblast growth factor-2 antisense gene product regulates pituitary cell growth and hormone production. Molecular Endocrinology 2001;15:589–99.CrossRef
Heaney, AP, Horwitz, GA, Wang, Z, Singson, R, Melmed, S. Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis. Nature Medicine 1999;5:1317–21.CrossRef
Gonsky, R, Herman, V, Melmed, S, Fagin, J. Transforming DNA sequences present in human prolactin-secreting pituitary tumors. Molecular Endocrinology 1991;5:1687–95.CrossRef
Shimon, I, Hüttner, A, Said, J, Spirna, OM, Melmed, S. Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell tumorigenesis and induces prolactin gene transcription. Journal of Clinical Investigation 1996;97:187–95.CrossRef
Itoh, N, Ornitz, DM. Evolution of the Fgf and Fgfr gene families. Trends in Genetics 2004;20:563–9.CrossRef
Ornitz, DM, Zu, J, Colvin, JS, et al. Receptor specificity of the fibroblast growth factor family. Journal of Biological Chemistry 1996;271:15 292–7.CrossRefGoogle ScholarPubMed
Luo, Y, Ye, S, Kan, M, McKeehan, WL.Structural specificity in a FGF7-affinity purified heparin octasaccharide required for formation of a complex with FGF7 and FGFR2IIIb. Journal of Cell Biochemistry 2006;97:1241–58.CrossRefGoogle Scholar
Thisse, B, Thisse, C, Weston, JA. Novel FGF receptor (Z-FGFR4) is dynamically expressed in mesoderm and neurectoderm during early zebrafish embryogenesis. Developmental Dynamics 1995;203:377–91.CrossRef
Thisse, B, Thisse, C. Functions and regulations of fibroblast growth factor signaling during embryonic development. Developmental Biology 2005;287:390–402.CrossRef
Baraniak, AP, Lasda, EL, Wagner, EJ, Garcia-Blanco, MA. A stem structure in fibroblast growth factor receptor 2 transcripts mediates cell-type-specific splicing by approximating intronic control elements. Molecular and Cellular Biology 2003;23:9327–37.CrossRef
De Moerlooze, L, Spencer-Dene, B, Revest, J, et al. An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development 2000;127:483–92.
Abbass, SAA, Asa, SL, Ezzat, S.Altered expression of fibroblast growth factor receptors in human pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1997;82:1160–6.CrossRefGoogle ScholarPubMed
Zhu, X, Lee, K, Asa, SL, Ezzat, S.Epigenetic silencing through DNA and histone methylation of fibroblast growth factor receptor 2 in neoplastic pituitary cells. American Journal of Pathology 2007;170:1618–28.CrossRefGoogle ScholarPubMed
Kondo, T, Zhu, X, Asa, SL, Ezzat, S. The cancer/testis antigen melanoma-associated antigen-A3/A6 is a novel target of fibroblast growth factor receptor 2-IIIb through histone H3 modifications in thyroid cancer. Clinical Cancer Research 2007;13:4713–20.CrossRef
Zhu, X, Asa, SL, Ezzat, S. Fibroblast growth factor 2 and estrogen control the balance of histone 3 modifications targeting MAGE-A3 in pituitary neoplasia. Clinical Cancer Research 2008;14:1984–96.CrossRef
Yu, S, Asa, SL, Weigel, RJ, Ezzat, S.Pituitary tumor AP-2alpha recognizes a cryptic promoter in intron 4 of fibroblast growth factor receptor 4. Journal of Biological Chemistry 2003;278:19 597–602.CrossRefGoogle ScholarPubMed
Ezzat, S, Zheng, L, Zhu, XF, Wu, GE, Asa, SL.Targeted expression of a human pituitary tumor-derived isoform of FGF receptor-4 recapitulates pituitary tumorigenesis. Journal of Clinical Investigation 2002;109:69–78.CrossRefGoogle ScholarPubMed
Ezzat, S, Zheng, L, Asa, SL. Pituitary tumor-derived fibroblast growth factor receptor 4 isoform disrupts neural cell-adhesion molecule/N-cadherin signaling to diminish cell adhesiveness:a mechanism underlying pituitary neoplasia. Molecular Endocrinology 2004;18:2543–52.CrossRef
Tateno, T, Asa, SL, Zheng, L, et al. The FGFR4-G388R polymorphism promotes mitochondrial STAT3 serine phosphorylation to facilitate pituitary growth hormone cell tumorigenesis. PLoS Genetics 2011;7:e10022400.
Hirohashi, S, Kanai, Y. Cell adhesion system and human cancer morphogenesis. Cancer Science 2003;94:575–81.CrossRef
Cavallaro, U, Schaffhauser, B, Christofori, G. Cadherins and the tumour progression:is it all in a switch? Cancer Letters 2002;176:123–8.
Cavallaro, U, Niedermeyer, J, Fuxa, M, Christofori, G. N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling. Nature Cell Biology 2001;3:650–7.CrossRef
Daniel, L, Trouillas, J, Renaud, W, et al. Polysialylated-neural cell adhesion molecule expression in rat pituitary transplantable tumors (spontaneous mammotropic transplantable tumor in Wistar-Furth rats) is related to growth rate and malignancy. Cancer Research 2000;60:80–5.
Fujimoto, I, Bruses, JL, Rutishauser, U.Regulation of cell adhesion by polysialic acid: effects on cadherin, immunoglobulin cell adhesion molecule, and integrin function and independence from neural cell adhesion molecule binding or signaling activity. Journal of Biological Chemistry 2001;276:31 745–51.CrossRefGoogle ScholarPubMed
Conacci-Sorrell, M, Zhurinsky, J, Ben Ze'ev, A.The cadherin-catenin adhesion system in signaling and cancer. Journal of Clinical Investigation 2002;109:987–91.CrossRefGoogle ScholarPubMed
Heinrich, CA, Lail-Trecker, MR, Peluso, JJ, White, BA. Negative regulation of N-cadherin-mediated cell-cell adhesion by the estrogen receptor signaling pathway in rat pituitary GH3 cells. Endocrine 1999;10:67–76.CrossRef
Qian, ZR, Li, CC, Yamasaki, H, et al. Role of E-cadherin, alpha-, beta-, and gamma-catenins, and p120 (cell adhesion molecules) in prolactinoma behavior. Modern Pathology 2002;15:1357–65.CrossRef
Mete, O, Ezzat, S, Asa, SL. Biomarkers of aggressive pituitary adenomas. Journal of Molecular Endocrinology 2012;49(2):R69–78.
Altas, M, Bayrak, OF, Ayan, E, et al. The effect of polymorphisms in the promoter region of the MMP-1 gene on the occurrence and invasiveness of hypophyseal adenoma. Acta Neurochirurgica 2010;152:1611–17.CrossRef
Georgopoulos, K. Haematopoietic cell fate decisions, chromatin regulation and ikaros. Nature Reviews Immunology 2002;2(3):162–74.CrossRef
Ezzat, S, Mader, R, Yu, SJ, et al. Ikaros integrates endocrine and immune system development. Journal of Clinical Investigation 2005;115:1021–9.
Ezzat, S, Mader, R, Fischer, S, et al. An essential role for the hematopoietic transcription factor Ikaros in hypothalamic-pituitary-mediated somatic growth. Proceedings of the National Academy of Sciences USA 2006;103(7):2214–19.CrossRef
Ezzat, S, Yu, SJ, Asa, SL. The zinc finger Ikaros transcription factor regulates pituitary growth hormone and prolactin gene expression through distinct effects on chromatin accessibility. Molecular Endocrinology 2005;19(4):1004–11.CrossRef
Ezzat, S, Yu, S, Asa, SL. Ikaros isoforms in human pituitary tumors: distinct localization, deacetylation, and activation of the 5’ FGFR4 Promoter. American Journal of Pathology 2003;163(3):1177–84.
Ezzat, S, Zhu, X, Loeper, S, Fischer, S, Asa, SL. Tumor-derived Ikaros 6 acetylates the Bcl-XL promoter to up-regulate a survival signal in pituitary cells. Molecular Endocrinology 2006;20(11):2976–86.CrossRef
Dorman, K, Shen, Z, Ezzat, S, Asa, SL, CtBP1 and Ikaros modulate pituitary tumor cell survival and response to hypoxia. Molecular Endocrinology 2012;26(3):447–57.
Loeper, S, Asa, SL, Ezzat, S. Ikaros modulates cholesterol uptake: a link between tumor suppression and differentiation. Cancer Research 2008;68:3715–23.CrossRef
Zhu, X, Lee, K, Asa, SL, Ezzat, S. Ikaros is regulated through multiple histone modifications and DNA methylation in the pituitary. Molecular Endocrinology 2007;21(5):1205–15.CrossRef
Zhu, X, Mao, X, Hurren, R, et al. DNA methyl-transferase 3B promotes epigenetic silencing through histone 3 chromatin modifications in pituitary cells. Journal of Clinical Endocrinology and Metabolism 2008;93:3610–17.
Vance, ML, Thorner, MO. Prolactinomas. Endocrinology and Metabolism Clinics of North America 1987;16:731–53.
Ezzat, S, Snyder, PJ, Young, WF, et al. Octreotide treatment of acromegaly. A randomized, multicenter study. Annals of Internal Medicine 1992;117:711–18.CrossRef
Riley, DJ, Nikitin, AY, Lee, WH. Adenovirus-mediated retinoblastoma gene therapy suppresses spontaneous pituitary melanotroph tumors in Rb+/– mice. Nature Medicine 1996;2:1316–21.CrossRef
Freese, A, During, MJ, Davidson, BL, et al. Transfection of human lactotroph adenoma cells with an adenovirus vector expressing tyrosine hydroxylase decreases prolactin release. Journal of Clinical Endocrinology and Metabolism 1996;81:2401–4.Google ScholarPubMed
Ezzat, S, Zheng, L, Winer, D, Asa, SL. Targeting N-cadherin through fibroblast growth factor receptor-4: distinct pathogenetic and therapeutic implications. Molecular Endocrinology 2006;20:2965–75.CrossRef

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

  • Mechanisms of pituitary tumorigenesis
    • By Shereen Ezzat, Department of Medicine, University of Toronto and the Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada, Sylvia L. Asa, Department of Pathology and Laboratory Medicine, University of Toronto, Department of Pathology, University Health Network, Toronto, Ontario, Canada
  • Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
  • Book: Molecular Oncology
  • Online publication: 05 February 2015
  • Chapter DOI: https://doi.org/10.1017/CBO9781139046947.059
Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • Mechanisms of pituitary tumorigenesis
    • By Shereen Ezzat, Department of Medicine, University of Toronto and the Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada, Sylvia L. Asa, Department of Pathology and Laboratory Medicine, University of Toronto, Department of Pathology, University Health Network, Toronto, Ontario, Canada
  • Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
  • Book: Molecular Oncology
  • Online publication: 05 February 2015
  • Chapter DOI: https://doi.org/10.1017/CBO9781139046947.059
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Mechanisms of pituitary tumorigenesis
    • By Shereen Ezzat, Department of Medicine, University of Toronto and the Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada, Sylvia L. Asa, Department of Pathology and Laboratory Medicine, University of Toronto, Department of Pathology, University Health Network, Toronto, Ontario, Canada
  • Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
  • Book: Molecular Oncology
  • Online publication: 05 February 2015
  • Chapter DOI: https://doi.org/10.1017/CBO9781139046947.059
Available formats
×