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

Emma Tucker, Andrea Buda, Nari Janghra, Jenny Baker, Joy Coad, Morganden Moorghan, Mike Havler, Peter Dettmar, Massimo Pignatelli

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13 Citations (Scopus)

Abstract

β-Catenin is a multifunctional protein originally identified as a component of the cadherin cellcell 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, p 120 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. Nondysplastic colonic epithelial cells revealed β-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 β-catenin immunoreactivity (39/41 and 38/41 both scored 3) with focal nuclear staining (14/41). Expression patterns for α-catenin, p120, 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.

Original languageEnglish
Pages (from-to)229-236
Number of pages8
JournalProceedings of the Nutrition Society
Volume62
Issue number1
DOIs
Publication statusPublished - Feb 1 2003

Keywords

  • Catenins
  • Colo-rectal carcinogenesis
  • Dimethylhydrazine model
  • E-cadherin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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  • Cite this

    Tucker, E., Buda, A., Janghra, N., Baker, J., Coad, J., Moorghan, M., Havler, M., Dettmar, P., & Pignatelli, M. (2003). Abnormalities of the cadherin-catenin complex in chemically-induced colo-rectal carcinogenesis. Proceedings of the Nutrition Society, 62(1), 229-236. https://doi.org/10.1079/PNS2003217