Implication of GST-pi expression in colon carcinogenesis

Yoshiro Niitsu, Tetsuji Takayama, Koji Miyanishi, Atsushi Nobuoka, Tsuyoshi Hayashi, Takaharu Nakajima, Sachie Miyake, Colin J. Henderson, Roland Wolf

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    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.

    Original languageEnglish
    Pages (from-to)287-290
    Number of pages4
    JournalChemico-Biological Interactions
    Issue number1-3
    Publication statusPublished - 28 Feb 2001


    • Aberrant crypt foci
    • knock out mouse
    • K-ras mutation
    • Deoxycholic acid

    Cite this

    Niitsu, Y., Takayama, T., Miyanishi, K., Nobuoka, A., Hayashi, T., Nakajima, T., Miyake, S., Henderson, C. J., & Wolf, R. (2001). Implication of GST-pi expression in colon carcinogenesis. Chemico-Biological Interactions, 133(1-3), 287-290.