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Abnormalities of the cadherin-catenin complex in chemically-induced colo-rectal carcinogenesis

Published online by Cambridge University Press:  05 March 2007

Emma Tucker ,
Andrea Buda ,
Nari Janghra ,
Jenny Baker ,
Joy Coad ,
Morganden Moorghan ,
Mike Havler ,
Peter Dettmar  and
Massimo Pignatelli
Emma Tucker
Affiliation:
University of Bristol, Division of Histopathology, Department of Pathology and Microbiology, School of Medical Sciences and Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW, UK
Andrea Buda
Affiliation:
University of Bristol, Division of Histopathology, Department of Pathology and Microbiology, School of Medical Sciences and Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW, UK
Nari Janghra
Affiliation:
University of Bristol, Division of Histopathology, Department of Pathology and Microbiology, School of Medical Sciences and Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW, UK
Jenny Baker
Affiliation:
University of Bristol, Division of Histopathology, Department of Pathology and Microbiology, School of Medical Sciences and Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW, UK
Joy Coad
Affiliation:
University of Bristol, Division of Histopathology, Department of Pathology and Microbiology, School of Medical Sciences and Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW, UK
Morganden Moorghan
Affiliation:
University of Bristol, Division of Histopathology, Department of Pathology and Microbiology, School of Medical Sciences and Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW, UK
Mike Havler
Affiliation:
Reckitt Benckiser Healthcare Ltd, Dansom Lane, Kingston upon Hull HU8 7DS, UK
Peter Dettmar
Affiliation:
Reckitt Benckiser Healthcare Ltd, Dansom Lane, Kingston upon Hull HU8 7DS, UK
Massimo Pignatelli*
Affiliation:
University of Bristol, Division of Histopathology, Department of Pathology and Microbiology, School of Medical Sciences and Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW, UK
*
*Corresponding author: Professor Massimo Pignatelli, fax +44 117 929 2440, massimo.pignatelli@bristol.ac.uk
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Abstract

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β-Catenin is a multifunctional protein originally identified as a component of the cadherin cell-cell adhesion complex. It also binds the adenomatous polyposis coli (APC) tumour suppressor which controls β-catenin cellular levels through its degradation. β-Catenin and/or APC mutations result in increased cytoplasmic β-catenin and nuclear translocation. The aim of the present study was to examine the expression and cellular localisation of α- and β-catenin, pi20 and E-cadherin in a chemically-induced mouse model of colo-rectal cancer using 1,2-dimethylhydrazine (DMH). Female Balb/C mice were injected subcutaneously with a solution providing 25 mg DMH base/kg body weight for 17 weeks. Animals were killed and tumours identified in the intestine with a dissecting microscope. Formalin-fixed paraffin-embedded sections of normal and dysplastic colonic mucosa were stained by an indirect avidin-biotin immunohistochemical technique using mouse monoclonal antibodies, and membranous, cytoplasmic and nuclear cellular localisation was assessed by light microscopy. Staining distribution scored as follows: 3, >90% positive epithelial cells; 2, >50% positive epithelial cells; 1, <50% positive epithelial cells. Non-dysplastic colonic epithelial cells revealed p-catenin expression at the membrane (33/41 scored 3), areas of cytoplasmic expression (24/41 scored 1) and no nuclear staining. Dysplastic colonic epithelium revealed increased membranous and cytoplasmic p-catenin immunoreactivity (39/41 and 38/41 both scored 3) with focal nuclear staining (14/41). Expression patterns for a-catenin, pi20, and E-cadherin were similar to β-catenin with increased membranous and cytoplasmic immunoreactivity in dysplastic mucosa, although no nuclear staining was observed. Increased cytoplasmic expression and nuclear localisation of β-catenin are consistent with a possible mutation in its gene, and this finding was in keeping with the mutational analysis of exon 3 by single-strand conformational polymorphism. Increased immunoreactivity of the other catenins also suggests further disruption in catenin regulation. In summary, alterations in the β-catenin expression and cellular localisation in the DMH-induced tumours are similar to those seen in human sporadic colo-rectal tumours. The DMH is therefore a useful model for studying the abnormalities of the E-cadherin-catenin pathway in colo-rectal carcinogenesis.

Keywords

E-cadherinCateninsColo-rectal carcinogenesisDimethylhydrazine model
Type
Session: Physiological aspects of fibre
Information
Proceedings of the Nutrition Society , Volume 62 , Issue 1 , February 2003 , pp. 229 - 236
Copyright
Copyright © The Nutrition Society 2003

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