Connexin43 is overexpressed in ApcMin/+‐mice adenomas and colocalises with COX‐2 in myofibroblasts
Open Access
- 10 June 2005
- journal article
- carcinogenesis
- Published by Wiley in International Journal of Cancer
- Vol. 116 (3), 351-358
- https://doi.org/10.1002/ijc.21025
Abstract
The expression of gap junction proteins, connexins, in the intestine and their role in tumorigenesis are poorly characterised. Truncating mutations in the tumour suppressor gene adenomatous polyposis coli (APC) are early and important events, both in inheritable (familial adenomatous polyposis, FAP) and spontaneous forms of intestinal cancer. Multiple intestinal neoplasia (Min) mice, a FAP model with inherited heterozygous mutation in Apc, spontaneously develop numerous intestinal adenomas. We recently reported reduced expression of connexin32 in Paneth cells of Min-mice. We further examine the expression of connexin43 (Cx43) and other connexins as a function of heterozygous and homozygous Apc mutation in normal intestinal tissues and adenomas of Min-mice. Qualitative analysis of connexin mRNA in intestine revealed a similar expression pattern in Min- and wild-type (wt) mice. Connexin26 and connexin40 proteins were found in equal amounts in Min and wt epithelia of large and small intestine, respectively. Interestingly, the connexin43 level was increased in the stroma of Min-mice adenomas, in close proximity to epithelial cells with nuclear β-catenin staining. Cx43 and COX-2 were located to the same areas of the adenomas, and immunostaining exhibited coexpression in the myofibroblasts. Prostaglandin E2 induces Cx43 expression and COX-2 is the rate-limiting enzyme in the prostaglandin synthesis. However, the COX-2-specific inhibitor, celecoxib, did not reduce Cx43 expression. Although both Cx43 and COX-2 are target genes for β-catenin, they were overexpressed in stromal cells but not in epithelial tumour cells. We hypothesise that gap junctions may be of importance in the transfer of signals between epithelium and stroma.This publication has 48 references indexed in Scilit:
- Truncated mouse adenomatous polyposis coli reduces connexin32 content and increases matrilysin secretion from Paneth cellsEuropean Journal of Cancer, 2004
- Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC The Journal of cell biology, 2003
- General suitability of techniques for in situ detection of apoptosis in small intestinal epitheliumThe Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology, 2003
- Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancerOncogene, 2002
- Autocrine Regulation of Myocyte Cx43 Expression by VEGFCirculation Research, 2002
- Prostaglandins Up-Regulate Vascular Endothelial Growth Factor Production through Distinct Pathways in Differentiated U937 CellsBiochemical and Biophysical Research Communications, 2000
- Differential expression of matrilysin and cyclooxygenase-2 in intestinal and colorectal neoplasmsMolecular Carcinogenesis, 1999
- APC mutations occur early during colorectal tumorigenesisNature, 1992
- Identification and characterization of the familial adenomatous polyposis coli geneCell, 1991
- Functional gap junctions in mouse small intestinal cryptsThe Anatomical Record, 1985