Aberrant accumulation of β-catenin protein because of mutation of either the β-catenin or adenomatous polyposis coli gene plays an essential role in the development of colorectal carcinoma. We established previously a stable clone of the rat small intestinal epithelial cell line IEC6, which is capable of inducing stabilized β-catenin protein lacking NH2-terminal glycogen synthase kinase-3β phosphorylation site under a strict control of the tetracycline-regulatory system. This clone, IEC6-TetOFFβ-catenin ΔN89, shows in vitro polypoid growth on the removal of doxycycline and seems to be an appropriate model for analyzing the molecular mechanisms of early intestinal carcinogenesis. Of >2000 protein spots displayed by newly developed two-dimensional difference gel electrophoresis, 22 were found to be up- or down-regulated on the induction of stabilized β-catenin. The majority of these proteins fell into two categories: (a) redox-status regulatory proteins and (b) cytoskeleton-associated proteins. Representatively, a key redox-status regulatory protein, manganese superoxide dismutase, up-regulated in IEC6 cells expressing stabilized β-catenin protein, was overexpressed in adenoma and adenocarcinoma cells of familial adenomatous polyposis patients in parallel with the accumulation of β-catenin. These results suggest that aberrant accumulation of β-catenin might contribute to colorectal carcinogenesis by affecting redox status in the mitochondria of intestinal epithelial cells.
|Number of pages||7|
|Publication status||Published - 2003 Aug 1|
ASJC Scopus subject areas
- Cancer Research