Proteomic analysis of intestinal epithelial cells expressing stabilized β-catenin

Masahiro Seike, Tadashi Kondo, Yasuharu Mori, Akihiko Gemma, Shoji Kudoh, Michiie Sakamoto, Tesshi Yamada, Setsuo Hirohashi

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34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4641-4647
Number of pages7
JournalCancer Research
Volume63
Issue number15
Publication statusPublished - 2003 Aug 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Seike, M., Kondo, T., Mori, Y., Gemma, A., Kudoh, S., Sakamoto, M., Yamada, T., & Hirohashi, S. (2003). Proteomic analysis of intestinal epithelial cells expressing stabilized β-catenin. Cancer Research, 63(15), 4641-4647.