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Implication of GST-pi expression in colon carcinogenesis

Implication of GST-pi expression in colon carcinogenesis

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Original languageEnglish
Pages287-290
Number of pages4
JournalChemico-Biological Interactions
Journal publication date28 Feb 2001
Journal number1-3
Volume133
DOIs
StatePublished

Abstract

Aberrant crypt foci (ACF) are precursors of colon adenoma which frequently develop into carcinoma in humans, as well as in animals. We found a close association between GST-pi over-expression and K-ras mutation in human ACF which was not incidental and, in fact, seemed to be a causal relationship as transfection of mutated K-ras enhanced the expression of GST-pi through the activation of TRE promoter. The function of thus enhanced GST-pi was proven to protect the colonic epithelium of ACF from the toxicity of bile salts (DCA) in both in vitro GST-pi transfection experiments and in vivo tumorigenesis experiments where GST-pi KO mice showed essentially no ACF or adenoma formation. Three results indicate that the sequential events of K-ras mutation and GST-pi over-expression are implicated in the early stages of colon carcinogenesis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

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