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

Research output: Contribution to journalArticle

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

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Catenins
Proteomics
Epithelial Cells
Oxidation-Reduction
Proteins
Carcinogenesis
Clone Cells
Two-Dimensional Difference Gel Electrophoresis
APC Genes
Glycogen Synthase Kinase 3
Adenomatous Polyposis Coli
Molecular Models
Doxycycline
Tetracycline
Cytoskeleton
Adenoma
Superoxide Dismutase
Colorectal Neoplasms
Mitochondria
Adenocarcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

Proteomic analysis of intestinal epithelial cells expressing stabilized β-catenin. / Seike, Masahiro; Kondo, Tadashi; Mori, Yasuharu; Gemma, Akihiko; Kudoh, Shoji; Sakamoto, Michiie; Yamada, Tesshi; Hirohashi, Setsuo.

In: Cancer Research, Vol. 63, No. 15, 01.08.2003, p. 4641-4647.

Research output: Contribution to journalArticle

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, vol. 63, no. 15, pp. 4641-4647.
Seike M, Kondo T, Mori Y, Gemma A, Kudoh S, Sakamoto M et al. Proteomic analysis of intestinal epithelial cells expressing stabilized β-catenin. Cancer Research. 2003 Aug 1;63(15):4641-4647.
Seike, Masahiro ; Kondo, Tadashi ; Mori, Yasuharu ; Gemma, Akihiko ; Kudoh, Shoji ; Sakamoto, Michiie ; Yamada, Tesshi ; Hirohashi, Setsuo. / Proteomic analysis of intestinal epithelial cells expressing stabilized β-catenin. In: Cancer Research. 2003 ; Vol. 63, No. 15. pp. 4641-4647.
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