TITLE

p16 and p27 are functionally correlated during the progress of hepatocarcinogenesis

AUTHOR(S)
Matsuda, Yasunobu; Ichida, Takafumi
PUB. DATE
December 2006
SOURCE
Medical Molecular Morphology;Dec2006, Vol. 39 Issue 4, p169
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The molecular mechanism of the cell-cycle machinery in hepatocellular carcinoma (HCC) has not yet been fully elucidated. Among the various types of cell-cycle regulators, p16 and p27 are now considered to be potent tumor suppressors. p16 is a G1-specific cell-cycle inhibitor that prevents the association of cyclin-dependent kinase (CDK) 4 and CDK6 with cyclin D1. Many studies have reported that p16 is inactivated not only in aggressive types of HCC but also in preneoplastic liver cirrhosis. In many cases of HCC, p16 is mainly inactivated by extensive CpG methylation, suggesting that epigenetic changes in the p16 gene may be important events during hepatocarcinogenesis. p27, an inhibitor of CDK2, is presently regarded as a potent adverse prognostic factor in many aggressive cancers. It should be noted that some cases of HCC show increased cell proliferation despite the expression of considerable amounts of p27. In these cases, p27 is inactivated by sequestration into cyclin D1–CDK4-containing complexes. Although the reason for the compositional changes in the p27-containing complexes is unclear, our experimental results indicate that loss of p16 following DNA methylation is closely related to the functional inactivation of p27 in HCC. We suggest that assessment of the p16 status may be useful for a precise prognostic prediction for individuals with HCCs expressing high levels of p27.
ACCESSION #
23512481

 

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