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.
Original language | English |
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Pages (from-to) | 287-290 |
Number of pages | 4 |
Journal | Chemico-Biological Interactions |
Volume | 133 |
Issue number | 1-3 |
DOIs | |
Publication status | Published - 28 Feb 2001 |
Keywords
- Aberrant crypt foci
- GST-PI EXPRESSION
- knock out mouse
- K-ras mutation
- Deoxycholic acid