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Reduced expression of p27 kip1 and increased hepatocyte proliferation in p53‐deficient mice
Author(s) -
Yang Chuanwei,
Sun Mingzeng,
Ilic Zoran,
Friedrich Thomas D.,
Sell Stewart
Publication year - 2003
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10086
Subject(s) - biology , cyclin , kinase , hepatocyte , cell cycle , cyclin e , cell growth , cyclin dependent kinase , cyclin d1 , regulation of gene expression , microbiology and biotechnology , cancer research , gene , genetics , in vitro
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.