Document Detail

Cell cycle regulators and human hepatocarcinogenesis.
MedLine Citation:
PMID:  9840120     Owner:  NLM     Status:  MEDLINE    
G1 phase progression of mammalian cells is mainly controlled by the cyclin-cyclin-dependent kinase (CDK)-CDK inhibitor-retinoblastoma protein (pRb) regulatory pathway. Cell cycle regulators controlling G1 phase progression are frequently involved in the carcinogenesis of many human cancer types. In hepatocellular carcinoma (HCC) the CDK inhibitor p16INK4 is predominantly inactivated by post-transcriptional regulation and p16INK4 inactivation participates in the early-stage of hepatocarcinogenesis and in disease progression. Reduced p21(WAF1/CIP1) expression, which is associated mainly with p53 gene mutation in HCCs, contributes to hepatocarcinogenesis. Reduced p27Kip1 expression is also frequently involved in HCC. The CDK inhibitors p16INK4, p21(WAF1/CIP1) and p27Kip1 are independently affected and a change in the expression of one or more of these inhibitors contributes to carcinogenesis of the majority (nearly 90%) of HCCs. Cyclin D1 amplification and overexpression play a role in the carcinogenesis of a subset (11-13%) of HCCs. Disruption of the regulatory system controlling G1 phase progression is a common event in human hepatocarcinogenesis. Further studies systematically analyzing the major regulators controlling G1 phase progression in a large cohort of HCCs will strengthen our understanding of the molecular mechanism underlying human hepatocarcinogenesis. Correcting alterations that have occurred in the G1 phase regulatory machinery may provide a novel weapon to treat and prevent HCC.
A M Hui; M Makuuchi; X Li
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Hepato-gastroenterology     Volume:  45     ISSN:  0172-6390     ISO Abbreviation:  Hepatogastroenterology     Publication Date:    1998 Sep-Oct
Date Detail:
Created Date:  1999-02-10     Completed Date:  1999-02-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8007849     Medline TA:  Hepatogastroenterology     Country:  GREECE    
Other Details:
Languages:  eng     Pagination:  1635-42     Citation Subset:  IM    
Second Department of Surgery, Faculty of Medicine, University of Tokyo, Japan.
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MeSH Terms
Carcinoma, Hepatocellular / physiopathology*
Cell Cycle Proteins / physiology*
Cyclin-Dependent Kinases / antagonists & inhibitors,  physiology
G1 Phase / physiology
Liver Neoplasms / physiopathology*
Reg. No./Substance:
0/Cell Cycle Proteins; EC Kinases

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