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Cell-based models to test the effects of milk-derived bioactives

Published online by Cambridge University Press:  15 December 2011

S. Purup  and
T. S. Nielsen
S. Purup*
Affiliation:
Department of Animal Science, Faculty of Science and Technology, Aarhus University, Blichers Allé 20, PO Box 50, DK-8830 Tjele, Denmark
T. S. Nielsen
Affiliation:
Department of Animal Science, Faculty of Science and Technology, Aarhus University, Blichers Allé 20, PO Box 50, DK-8830 Tjele, Denmark
*
†E-mail: stig.purup@agrsci.dk
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Abstract

The life science industries have a strong interest in screening for novel bioactives in complex mixtures like milk and dairy products. Food bioactives are not only important for public health in general, but also have potential therapeutic applications for the treatment of a number of diseases. To identify these novel bioactives, establishment of robust screening assays is essential. The use of in vitro cell-based models for screening and testing have the advantage that several concentrations of mixtures or specific compounds can be assayed at the same time in cells from specific tissues. Primary cell cultures from target organs or established cell lines can be used to identify the most sensitive cells. In addition, a large number of transfected cell lines with very specific sensitivities have been developed. Different endpoints inherent to basal or more sophisticated cellular functions can be investigated, such as cell viability, apoptosis, migration, intracellular signalling, regulation of gene expression, morphology and metabolic alterations. The gastrointestinal tract is an obvious target for bioactive molecules delivered through milk and dairy products, because it lies at the interface between dietary components in the lumen and the internal processes of the host. Identification of bioactive factors that affects proliferation or migration of epithelial cells may have potential applications in promoting gastrointestinal health in both humans and animals. The mammary gland is another target organ of considerable interest since it has been estimated that up to 50% of all newly diagnosed breast cancers may be related to dietary factors. A large number of gastrointestinal and mammary epithelial cell lines are commercially available, but in order to study some cellular functions, primary cultures of freshly isolated cells are often preferred, as established cell lines do not always express specialised properties in culture.

Keywords

cell-based modelsbioactivitymilk-derived bioactives
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animal , Volume 6 , Issue 3: 61th EAAP Annual Meeting, 2010, Heraklion, Greece: 10th International Workshop on Biology of Lactation in Farm Animals (BOLFA) and Session “Evolution of mammary gland and milk secretion: consequences for lactation in farm animals” , 27 January 2012 , pp. 423 - 432
Copyright
Copyright © The Animal Consortium 2011

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References

Akers, RM, McFadden, TB, Purup, S, Vestergaard, M, Sejrsen, K, Capuco, AV 2000. Local IGF-I axis in peripubertal ruminant mammary development. Journal of Mammary Gland Biology and Neoplasia 5, 43–51.CrossRefGoogle ScholarPubMed
Andersen, C, Nielsen, TS, Purup, S, Kristensen, T, Eriksen, J, Søegaard, K, Sørensen, J, Fretté, XC 2009. Phyto-oestrogens in herbage and milk from cows grazing white clover, red clover, lucerne or chicory-rich pastures. Animal 3, 1189–1195.CrossRefGoogle ScholarPubMed
Antignac, JP, Gaudin-Hirret, I, Naegeli, H, Cariou, R, Elliott, C, Le Bizec, B 2009. Multi-functional sample preparation procedure for measuring phytoestrogens in milk, cereals, and baby-food by liquid-chromatography tandem mass spectrometry with subsequent determination of their estrogenic activity using transcriptomic assay. Analytica Chimica Acta 637, 55–63.Google Scholar
Baldi, A, Losio, MN, Cheli, F, Rebucci, R, Sangalli, L, Fusi, E, Bertasi, B, Pavoni, E, Carli, S, Politis, I 2004. Evaluation of the protective effects of alpha-tocopherol and retinol against ochratoxin A cytotoxicity. British Journal of Nutrition 91, 507–512.CrossRefGoogle ScholarPubMed
Barrientos, S, Stojadinovic, O, Golinko, MS, Brem, H, Tomic-Canic, M 2008. Growth factors and cytokines in wound healing. Wound Repair and Regeneration 16, 585–601.Google Scholar
Belford, DA, Rogers, ML, Francis, GL, Payne, C, Ballard, FJ, Goddard, C 1997. Platelet-derived growth factor, insulin-like growth factors, fibroblast growth factors and transforming growth factor beta do not account for the cell growth activity present in bovine milk. Journal of Endocrinology 154, 45–55.Google Scholar
Benassayag, C, Perrot-Applanat, M, Ferre, F 2002. Phytoestrogens as modulators of steroid action in target cells. Journal of Chromatography B 777, 233–248.Google Scholar
Bernard-Gallon, DJ, Satih, S, Chalabi, N, Rabiau, N, Bosviel, R, Fontana, L, Bignon, YJ 2010. Phytoestrogens regulate the expression of genes involved in different biological processes in BRCA2 knocked down MCF-7, MDA-MB-231 and MCF-10a cell lines. Oncology Reports 23, 647–653.Google ScholarPubMed
Berry, SD, Weber Nielsen, MS, Sejrsen, K, Pearson, RE, Boyle, PL, Akers, RM 2003. Use of an immortalized bovine mammary epithelial cell line (MAC-T) to measure the mitogenic activity of extracts from heifer mammary tissue: effects of nutrition and ovariectomy. Domestic Animal Endocrinology 25, 245–253.Google Scholar
Brooks, SA, Carter, TM, Royle, L, Harvey, DJ, Fry, SA, Kinch, C, Dwek, RA, Rudd, PM 2008. Altered glycosylation of proteins in cancer: what is the potential for new anti-tumour strategies. Anticancer Agents in Medical Chemistry 8, 2–21.Google Scholar
Bruzelius, K, Purup, S, James, P, Onning, G, Akesson, B 2008. Biosynthesis of selenoproteins in cultured bovine mammary cells. Journal of Trace Elements in Medicine and Biology 22, 224–233.CrossRefGoogle ScholarPubMed
Calabrese, EJ 2010. Hormesis is central to toxicology, pharmacology and risk assessment. Human and Experimental Toxicology 29, 249–261.Google Scholar
Calabrese, EJ, Baldwin, LA 1998. Hormesis as a biological hypothesis. Environmental Health Perspectives 106 (suppl. 1), 357–362.Google ScholarPubMed
Capuco, AV, Ellis, S, Wood, DL, Akers, RM, Garrett, W 2002. Postnatal mammary ductal growth: three-dimensional imaging of cell proliferation, effects of estrogen treatment, and expression of steroid receptors in prepubertal calves. Tissue and Cell 34, 143–154.CrossRefGoogle ScholarPubMed
Cencic, A, Langerholc, T 2010. Functional cell models of the gut and their applications in food microbiology – a review. International Journal of Food Microbiology 141 (suppl. 1), S4–S14.Google Scholar
Cheli, F, Baldi, A, Dell'Orto, V, Zavizion, B, Politis, I 2001. Pattern of protein production by mammary epithelial cells cultured on membrane inserts. Canadian Journal of Animal Science 81, 285–287.CrossRefGoogle Scholar
Cheli, F, Politis, I, Rossi, L, Fusi, E, Baldi, A 2003. Effects of retinoids on proliferation and plasminogen activator expression in a bovine mammary epithelial cell line. Journal of Dairy Research 70, 367–372.CrossRefGoogle Scholar
Chopra, DP, Dombkowski, AA, Stemmer, PM, Parker, GC 2010. Intestinal epithelial cells in vitro. Stem Cells and Development 19, 131–142.Google Scholar
Clare, DA, Swaisgood, HE 2000. Bioactive milk peptides: a prospectus. Journal of Dairy Science 83, 1187–1195.CrossRefGoogle ScholarPubMed
Cohick, WS, Turner, JD 1998. Regulation of IGF binding protein synthesis by a bovine mammary epithelial cell line. Journal of Endocrinology 157, 327–336.Google Scholar
Committee on Toxicity 2003. Phytoestrogens and health. The Food Standards Agency (Chairman, Woods HF), London, UK.Google Scholar
Courant, F, Antignac, JP, Maume, D, Monteau, F, Andre, F, Le, BB 2007. Determination of naturally occurring oestrogens and androgens in retail samples of milk and eggs. Food Additives and Contaminants 24, 1358–1366.Google Scholar
Delie, F, Rubas, W 1997. A human colonic cell line sharing similarities with enterocytes as a model to examine oral absorption: advantages and limitations of the Caco-2 model. Critical Reviews in Therapeutic Drug Carrier Systems 14, 221–286.CrossRefGoogle Scholar
Dip, R, Lenz, S, Antignac, JP, Le Bizec, B, Gmuender, H, Naegeli, H 2008. Global gene expression profiles induced by phytoestrogens in human breast cancer cells. Endocrine-Related Cancer 15, 161–173.CrossRefGoogle ScholarPubMed
Doll, R 1992. The lessons of life: keynote address to the nutrition and cancer conference. Cancer Reseach 52, S2024–S2029.Google Scholar
Ellis, S, Purup, S, Sejrsen, K, Akers, RM 2000. Growth and morphogenesis of epithelial cell organoids from peripheral and medial mammary parenchyma of prepubertal heifers. Journal of Dairy Science 83, 952–961.CrossRefGoogle ScholarPubMed
Ernens, I, Clegg, R, Schneider, YJ, Larondelle, Y 2007. Short communication: ability of cultured mammary epithelial cells in a bicameral system to secrete milk fat. Journal of Dairy Science 90, 677–681.CrossRefGoogle Scholar
Farlow, DW, Xu, X, Veenstra, TD 2009. Quantitative measurement of endogenous estrogen metabolites, risk-factors for development of breast cancer, in commercial milk products by LC-MS/MS. Journal of Chromatography B 877, 1327–1334.Google Scholar
Fiedorowicz, E, Jarmolowska, B, Iwan, M, Kostyra, E, Obuchowicz, R, Obuchowicz, M 2011. The influence of mu-opioid receptor agonist and antagonist peptides on peripheral blood mononuclear cells (PBMCs). Peptides 32, 707–712.Google Scholar
Fusi, E, Rebucci, R, Pecorini, C, Rossi, L, D'Ambrosio, F, Baldi, A 2008. Evaluation of the damage induced by ochratoxin A and the protective role of alpha-tocopherol in cultured bovine mammary epithelial cells. Veterinary Research Communications 32 (suppl. 1), S343–S345.CrossRefGoogle ScholarPubMed
Gibson, RA 2011. Milk fat and health consequences. Nestle Nutrition Workshop Series. Paediatric Programme 67, 197–207.Google Scholar
Hansen, SL, Purup, S, Christensen, LP 2003. Bioactivity of falcarinol and the influence of processing and storage on its content in carrots (Daucus carota L.). Journal of the Science of Food and Agriculture 83, 1010–1017.CrossRefGoogle Scholar
Hartmann, S, Lacorn, M, Steinhart, H 1998. Natural occurrence of steroid hormones in food. Food Chemistry 62, 7–20.Google Scholar
Hata, I, Higashiyama, S, Otani, H 1998. Identification of a phosphopeptide in bovine αs1-casein digest as a factor influencing proliferation and immunoglobulin production in lymphocyte cultures. Journal of Dairy Research 65, 569–578.Google Scholar
Hilakivi-Clarke, L, Cho, E, deAssis, S, Olivo, S, Ealley, E, Bouker, KB, Welch, JN, Khan, G, Clarke, R, Cabanes, A 2001. Maternal and prepubertal diet, mammary development and breast cancer risk. Journal of Nutrition 131, 154S–157S.CrossRefGoogle ScholarPubMed
Hirai, C, Ichiba, H, Saito, M, Shintaku, H, Yamano, T, Kusuda, S 2002. Trophic effect of multiple growth factors in amniotic fluid or human milk on cultured human fetal small intestinal cells. Journal of Pediatric Gastroenterology and Nutrition 34, 524–528.Google Scholar
Hoikkala, A, Mustonen, E, Saastamoinen, I, Jokela, T, Taponen, J, Saloniemi, H, Wahala, K 2007. High levels of equol in organic skimmed Finnish cow milk. Molecular Nutrition and Food Research 51, 782–786.CrossRefGoogle ScholarPubMed
Huynh, HT, Robitaille, G, Turner, JD 1991. Establishment of bovine mammary epithelial cells (MAC-T): an in vitro model for bovine lactation. Experimental Cell Research 197, 191–199.CrossRefGoogle Scholar
Ichiba, H, Kusuda, S, Itagane, Y, Fujita, K, Issiki, G 1992. Measurement of growth promoting activity in human milk using a fetal small intestinal cell line. Biology of the Neonate 61, 47–53.CrossRefGoogle ScholarPubMed
Ip, MM, Masso-Welch, PA, Shoemaker, SF, Shea-Eaton, WK, Ip, C 1999. Conjugated linoleic acid inhibits proliferation and induces apoptosis of normal rat mammary epithelial cells in primary culture. Experimental Cell Research 250, 22–34.Google Scholar
Kawahara, T, Katayama, D, Otani, H 2004. Effect of b-casein (1–28) on proliferative responses and secretory functions of human immunocompetent cell lines. Bioscience, Biotechnology, and Biochemistry 68, 2091–2095.Google Scholar
Kawamura, N, Miki, K, Kurokawa, K, Kojima, I 1994. Enhancement by tocoretinate of epidermal growth factor-induced DNA synthesis in human intestinal epithelial cells. Digestive Diseases and Sciences 39, 2191–2196.Google Scholar
Keating, AF, Zhao, FQ, Finucane, KA, Glimm, DR, Kennelly, JJ 2008. Effect of conjugated linoleic acid on bovine mammary cell growth, apoptosis and stearoyl Co-A desaturase gene expression. Domestic Animal Endocrinology 34, 284–292.Google Scholar
King, RA, Mano, MM, Head, RJ 1998. Assessment of isoflavonoid concentrations in Australian bovine milk samples. Journal of Dairy Research 65, 479–489.Google Scholar
Kitazawa, H, Yonezawa, K, Tohno, M, Shimosato, T, Kawai, Y, Saito, T, Wang, JM 2007. Enzymatic digestion of the milk protein beta-casein releases potent chemotactic peptide(s) for monocytes and macrophages. International Immunopharmacology 7, 1150–1159.Google Scholar
Klagsbrun, M, Neumann, J 1979. The serum-free growth of Balb/c 3T3 cells in medium supplemented with bovine colostrum. Journal of Supramolecular Structure 11, 349–359.Google Scholar
Klagsbrun, M, Shing, Y 1984. Growth-promoting factors in human and bovine milk. Growth Maturation Factors 2, 161–192.Google Scholar
Kozlowski, M, Gajewska, M, Majewska, A, Jank, M, Motyl, T 2009. Differences in growth and transcriptomic profile of bovine mammary epithelial monolayer and three-dimensional cell cultures. Journal of Physiology and Pharmacology 60 (suppl. 1), 5–14.Google Scholar
Lametsch, R, Rasmussen, JT, Johnsen, LB, Purup, S, Sejrsen, K, Petersen, TE, Heegaard, CW 2000. Structural characterization of the fibroblast growth factor-binding protein purified from bovine prepartum mammary gland secretion. Journal of Biological Chemistry 275, 19469–19474.Google Scholar
Malekinejad, H, Scherpenisse, P, Bergwerff, AA 2006. Naturally occurring estrogens in processed milk and in raw milk (from gestated cows). Journal of Agricultural and Food Chemistry 54, 9785–9791.Google Scholar
Martin, JH, Crotty, S, Nelson, PN 2007. Phytoestrogens: perpetrators or protectors? Future Oncology 3, 307–318.CrossRefGoogle ScholarPubMed
Matitashvili, E, Bauman, DE 1999. Culture of primary bovine mammary epithelial cells. In Vitro Cell and Developmental Biology – Animal 35, 431–434.Google Scholar
Matitashvili, E, Bauman, DE 2001. Synthesis of extracellular matrix proteins in bovine mammary epithelial cells. In Vitro Cell and Developmental Biology – Animal 37, 629–632.Google Scholar
Meisel, H, Gunther, S 1998. Food proteins as precursors of peptides modulating human cell activity (short communication). Nahrung 42, 175–176.Google Scholar
Michaelidou, A, Steijns, J 2006. Nutritional and technological aspects of minor bioactive components in milk and whey: growth factors, vitamins and nucleotides. International Dairy Journal 16, 1421–1426.Google Scholar
Moller, NP, Scholz-Ahrens, KE, Roos, N, Schrezenmeir, J 2008. Bioactive peptides and proteins from foods: indication for health effects. European Journal of Nutrition 47, 171–182.Google Scholar
Nielsen, TS, Norgaard, JV, Purup, S, Frette, XC, Bonefeld-Jorgensen, EC 2009. Estrogenic activity of bovine milk high or low in equol using immature mouse uterotrophic responses and an estrogen receptor transactivation assay. Cancer Epidemiology 33, 61–68.CrossRefGoogle ScholarPubMed
Norup, LR, Purup, S, Sejrsen, K 1997. Mitogenic effects of serum from heifers of different ages on proliferation of mammary epithelial cells in collagen gel culture. In Book of abstracts of the 48th Annual Meeting of the EAAP (ed. JAM van Arendonk), p. 183. Wageningen Press, Wageningen, The Netherlands.Google Scholar
Ou, L, Wu, Y, Ip, C, Meng, X, Hsu, YC, Ip, MM 2008. Apoptosis induced by t10,c12-conjugated linoleic acid is mediated by an atypical endoplasmic reticulum stress response. Journal of Lipid Research 49, 985–994.Google Scholar
Park, Y, Allen, KG, Shultz, TD 2000. Modulation of MCF-7 breast cancer cell signal transduction by linoleic acid and conjugated linoleic acid in culture. Anticancer Research 20, 669–676.Google Scholar
Pecorini, C, Sassera, D, Rebucci, R, Saccone, F, Bandi, C, Baldi, A 2010. Evaluation of the protective effect of bovine lactoferrin against lipopolysaccharides in a bovine mammary epithelial cell line. Veterinary Research Communications 34, 267–276.CrossRefGoogle Scholar
Peterson, DG, Matitashvili, EA, Bauman, DE 2004. The inhibitory effect of trans-10, cis-12 CLA on lipid synthesis in bovine mammary epithelial cells involves reduced proteolytic activation of the transcription factor SREBP-1. Journal of Nutrition 134, 2523–2527.CrossRefGoogle ScholarPubMed
Pocock, VJ, Sales, GD, Milligan, SR 2002. Comparison of the oestrogenic effects of infant milk formulae, oestradiol and the phytoestrogen coumestrol delivered continuously in the drinking water to ovariectomised mice. Food and Chemical Toxicology 40, 643–651.Google Scholar
Purup, S, Sejrsen, K, Akers, RM 1993a. Influence of oestradiol on insulin-like growth factor (IGF-1) stimulation of DNA synthesis in mammary gland explants from intact and ovariectomized prepubertal heifers. Livestock Production Science 35, 182.Google Scholar
Purup, S, Sejrsen, K, Foldager, J, Akers, RM 1993b. Effect of exogenous bovine growth hormone and ovariectomy on prepubertal mammary growth, serum hormones and acute in-vitro proliferative response of mammary explants from Holstein heifers. Journal of Endocrinology 139, 19–26.Google Scholar
Purup, S, Jensen, SK, Sejrsen, K 1999. Differential effects of vitamin A metabolites on proliferation of bovine mammary epithelial cells in collagen gel culture. South African Journal of Animal Science 29, 291–293.Google Scholar
Purup, S, Jensen, SK, Sejrsen, K 2001. Differential effects of retinoids on proliferation of bovine mammary epithelial cells in collagen gel culture. Journal of Dairy Research 68, 157–164.Google Scholar
Purup, S, Sandowski, Y, Sejrsen, K 1995. Endocrine effect of IGF-1 on mammary growth in prepubertal heifers. In Intercellular signalling in the mammary gland (ed. CJ Wilde, M Peaker and CH Knight), pp. 93–94. Plenum Press Ltd., New York, NY, USA.CrossRefGoogle Scholar
Purup, S, Vestergaard, M, Pedersen, O, Sejrsen, K 2007. Biological activity of bovine milk on proliferation of human intestinal cells. Journal of Dairy Research 74, 58–65.Google Scholar
Purup, S, Vestergaard, M, Weisbjerg, MR, Hvelplund, T, Sejrsen, K 2002. Possible role of enterolactone on mammary development and lactation in cattle. Journal of Dairy Science 85, 9–10.Google Scholar
Purup, S, Vestergaard, M, Weber, MS, Plaut, K, Akers, RM, Sejrsen, K 2000. Involvement of growth factors in the regulation of pubertal mammary growth in cattle. In Advances in experimental medicine and biology, biology of the mammary gland (ed. R Clegg and J Mol), pp. 27–43. Kluwer Academic/Plenum Press, London, UK.Google Scholar
Purup, S, Hansen-Møller, J, Sejrsen, K, Christensen, LP, Lykkesfeld, AE, Leffers, H, Skakkebaek, NE 2005. Increased phytoestrogen content in organic milk and the biological importance. Newsletter from Danish Research Centre for Organic Farming, June 2005, no. 2. Danish Research Centre for Organic Farming, Tjele, Denmark.Google Scholar
Rogers, ML, Belford, DA, Francis, GL, Ballard, FJ 1995. Identification of fibroblast growth factors in bovine cheese whey. Journal of Dairy Research 62, 501–507.Google Scholar
Rusu, D, Drouin, R, Pouliot, Y, Gauthier, S, Poubelle, PE 2010. A bovine whey protein extract stimulates human neutrophils to generate bioactive IL-1Ra through a NF-kappaB- and MAPK-dependent mechanism. Journal of Nutrition 140, 382–391.CrossRefGoogle ScholarPubMed
Sejrsen, K, Pedersen, LO, Vestergaard, M, Purup, S 2000. Biological activity of bovine milk: contribution of IGF-I and IGF binding proteins. Livestock Production Science 70, 79–85.CrossRefGoogle Scholar
Seltana, A, Basora, N, Beaulieu, JF 2010. Intestinal epithelial wound healing assay in an epithelial-mesenchymal co-culture system. Wound Repair and Regeneration 18, 114–122.Google Scholar
Shah, NP 2000. Effects of milk-derived bioactives: an overview. British Journal of Nutrition 84 (suppl. 1), S3–S10.Google Scholar
Shin, K, Fogg, VC, Margolis, B 2006. Tight junctions and cell polarity. Annual Review of Cell and Developmental Biology 22, 207–235.Google Scholar
Smits, E, Burvenich, C, Guidry, AJ, Heyneman, R, Massart-Leën, 1999. Diapedesis across mammary epithelium reduces phagocytic and oxidative burst of bovine neutrophils. Veterinary Immunology and Immunopathology 68, 169–176.Google Scholar
Smits, E, Cifrian, E, Guidry, AJ, Rainard, P, Burvenich, C, Paape, MJ 1996. Cell culture system for studying bovine neutrophil diapedesis. Journal of Dairy Science 79, 1353–1360.Google Scholar
Sorensen, BM, Chris, KE, Murdoch, GK, Keating, AF, Cruz-Hernandez, C, Wegner, J, Kennelly, JJ, Okine, EK, Weselake, RJ 2008. Effect of CLA and other C18 unsaturated fatty acids on DGAT in bovine milk fat biosynthetic systems. Lipids 43, 903–912.Google Scholar
Steinshamn, H, Purup, S, Thuen, E, Hansen-Moller, J 2008. Effects of clover-grass silages and concentrate supplementation on the content of phytoestrogens in dairy cow milk. Journal of Dairy Science 91, 2715–2725.Google Scholar
Strange, KS, Wilkinson, D, Emerman, JT 2002. Mitogenic properties of insulin-like growth factors I and II, insulin-like growth factor binding protein-3 and epidermal growth factor on human breast epithelial cells in primary culture. Breast Cancer Research and Treatment 75, 203–212.Google Scholar
Sturm, A, Dignass, AU 2008. Epithelial restitution and wound healing in inflammatory bowel disease. World Journal of Gastroenterology 14, 348–353.Google Scholar
Swanson, KM, Stelwagen, K, Dobson, J, Henderson, HV, Davis, SR, Farr, VC, Singh, K 2009. Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model. Journal of Dairy Science 92, 117–129.Google Scholar
Takeda, T, Sakata, M, Minekawa, R, Yamamoto, T, Hayashi, M, Tasaka, K, Murata, Y 2004. Human milk induces fetal small intestinal cell proliferation – involvement of a different tyrosine kinase signaling pathway from epidermal growth factor receptor. Journal of Endocrinology 181, 449–457.Google Scholar
Thorn, SR, Purup, S, Cohick, WS, Vestergaard, M, Sejrsen, K, Boisclair, YR 2006. Leptin does not act directly on mammary epithelial cells in prepubertal dairy heifers. Journal of Dairy Science 89, 1467–1477.CrossRefGoogle Scholar
Thorn, SR, Purup, S, Vestergaard, M, Sejrsen, K, Meyer, MJ, Van Amburgh, ME, Boisclair, YR 2008. Regulation of mammary parenchymal growth by the fat pad in prepubertal dairy heifers: role of inflammation-related proteins. Journal of Endocrinology 196, 539–546.Google Scholar
Vachon, PH, Simoneau, A, Herring-Gillam, FE, Beaulieu, JF 1995. Cellular fibronectin expression is down-regulated at the mRNA level in differentiating human intestinal epithelial cells. Experimental Cell Research 216, 30–34.Google Scholar
Wagner, CL, Forsythe, DW, Wagner, MT 1998. The effect of recombinant TGFalpha, human milk, and human milk macrophage media on gut epithelial proliferation is decreased in the presence of a neutralizing TGFalpha antibody. Biology of the Neonate 74, 363–371.Google Scholar
Wang, Y, Baumrucker, CR 2010. Retinoids, retinoid analogs, and lactoferrin interact and differentially affect cell viability of 2 bovine mammary cell types in vitro. Domestic Animal Endocrinology 39, 10–20.CrossRefGoogle ScholarPubMed
Wang, LS, Huang, YW, Liu, S, Yan, P, Lin, YC 2008. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue. BMC Cancer 8, 208.Google Scholar
Weber, MS, Purup, S, Vestergaard, M, Akers, RM, Sejrsen, K 1997. Contribution of insulin-like-growth factor-I (IGF-I) to the mitogenic activity in mammary tissue of prepubertal dairy heifers. Journal of Dairy Science 80 (suppl. 1), 205.Google Scholar
Weber, MS, Purup, S, Vestergaard, M, Akers, RM, Sejrsen, K 2000. Nutritional and somatotropin regulation of the mitogenic response of mammary cells to mammary tissue extracts. Domestic Animal Endocrinology 18, 159–164.Google Scholar
Weber, MS, Purup, S, Vestergaard, M, Ellis, SE, Scndergard-Andersen, J, Akers, RM, Sejrsen, K 1999. Contribution of insulin-like growth factor (IGF)-I and IGF-binding protein-3 to mitogenic activity in bovine mammary extracts and serum. Journal of Endocrinology 161, 365–373.Google Scholar
Weng, XH, Beyenbach, KW, Quaroni, A 2005. Cultured monolayers of the dog jejunum with the structural and functional properties resembling the normal epithelium. American Journal of Physiology – Gastrointestinal Liver Physiology 288, G705–G717.Google Scholar
Woodward, TL, Turner, JD, Hung, HT, Zhao, X 1996. Inhibition of cellular proliferation and modulation of insulin-like growth factor binding proteins by retinoids in a bovine mammary epithelial cell line. Journal of Cell Physiology 167, 488–499.Google Scholar
Zarzynska, J, Gajewska, M, Motyl, T 2005. Effects of hormones and growth factors on TGF-beta1 expression in bovine mammary epithelial cells. Journal of Dairy Research 72, 39–48.Google Scholar
Zavizion, B, van Duffelen, M, Schaeffer, W, Politis, I 1996. Establishment and characterization of a bovine mammary epithelial cell line with unique properties. In Vitro Cell and Developmental Biology – Animal 32, 138–148.Google Scholar
Zhang, J, Warren, MA, Shoemaker, SF, Ip, MM 2007. NFkappaB1/p50 is not required for tumor necrosis factor-stimulated growth of primary mammary epithelial cells: implications for NFkappaB2/p52 and RelB. Endocrinology 148, 268–278.CrossRefGoogle Scholar
Zhou, Y, Capuco, AV, Jiang, H 2008. Involvement of connective tissue growth factor (CTGF) in insulin-like growth factor-I (IGF1) stimulation of proliferation of a bovine mammary epithelial cell line. Domestic Animal Endocrinology 35, 180–189.Google Scholar