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Reduced expression of p27kip1 and increased hepatocyte proliferation in p53-deficient mice

✍ Scribed by Chuanwei Yang; Mingzeng Sun; Zoran Ilic; Thomas D. Friedrich; Stewart Sell

Publisher
John Wiley and Sons
Year
2002
Tongue
English
Weight
244 KB
Volume
36
Category
Article
ISSN
0899-1987

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✦ Synopsis

Abstract

Livers from wild‐type and p53‐deficient mice were analyzed for the expression of cell‐cycle regulatory proteins in an attempt to determine the mechanism for the increased proliferation of liver cells in p53‐deficient mice associated with enhanced susceptibility to aflatoxin‐induced liver cancer. The most striking difference found was a significant reduction of the cyclin‐dependent kinase inhibitor p27^kip1^ in the livers of 3‐mo‐old p53−/− mice, whereas only small changes were found in the expression of cyclins, cyclin‐dependent kinases, and the inhibitors p21^cip1^ and p16^ink4a^. Relative to wild‐type liver, the amounts of p27^kip1^ mRNA were reduced at both 1 and 3 mo, whereas the levels of p27^kip1^ protein were decreased only at 3 mo. These results identify an uncharacterized link between the expression of p53 and p27^kip1^ that may involve both transcriptional and post‐transcriptional regulation and allow hepatocytes to continue to proliferate after 3 wk of age. We postulate that this increased proliferation leads to increased susceptibility to aflatoxin‐induced hepatocarcinogenesis. © 2002 Wiley‐Liss, Inc.

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