Hepatocellular Carcinoma Cell Cycle: Study of Long-Evans Cinnamon Rats

Amplification found in a number of cyclin genes, especially in cyclin D and E, is an important event process that takes place in cancers, including hepatocellular carcinoma (HCC). The activities of a wide range of cell cycle-related kinases remain obscure in HCC. The purpose of the present study is...

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Bibliographic Details
Published in:Hepatology (Baltimore, Md.) Md.), 2000-10, Vol.32 (4), p.711-720
Main Authors: Masaki, Tsutomu, Shiratori, Yasushi, Rengifo, William, Igarashi, Kouichi, Matsumoto, Kouzou, Nishioka, Mikio, Hatanaka, Yoshio, Omata, Masao
Format: Article
Language:English
Subjects:
Animal tumors. Experimental tumors
Animals
Biological and medical sciences
Blotting, Western
Cell Cycle
Cell Cycle Proteins - analysis
Cyclin A - analysis
Cyclin D1 - analysis
Cyclin E - analysis
Cyclin-Dependent Kinases - analysis
Cyclins - analysis
Experimental digestive system and abdominal tumors
Liver Neoplasms, Experimental - pathology
Medical sciences
Rats
Rats, Long-Evans
Rats, Wistar
Tumors
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Summary:Amplification found in a number of cyclin genes, especially in cyclin D and E, is an important event process that takes place in cancers, including hepatocellular carcinoma (HCC). The activities of a wide range of cell cycle-related kinases remain obscure in HCC. The purpose of the present study is to determine the cyclins and kinase activities of HCC in Long-Evans Cinnamon (LEC) rats. Cyclin D1, E, A, H, Cdk1(cyclin-dependent kinase; Cdc2), Cdk4, and Cdk6 protein levels were determined by Western blot analysis at different pathologic stages of liver tissues exhibiting HCC. Enzymatic activities of cyclin D1, E, A, Cdk4, Cdk6, Cdc2, Cdk7, and Wee1 kinase were measured by in-gel kinase assay. Protein levels and kinase activities of cyclin D1, E, Cdk4, cyclin A, and Wee1 increased proportionally with the development of HCC, especially in the transition process from chronic hepatitis to HCC. Although Cdc2 kinase activity was found to increase slightly from normal liver to chronic hepatitis, its activity remained unchanged in the process from chronic hepatitis to HCC. Cdk6 and Cdk7 activities remained unchanged in the process from normal liver to HCC. These data suggest that the increase in Cdc2 kinase may play a role in the process from normal liver to chronic hepatitis, whereas the predominant increase in cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 suggests involvement not only in the process from normal liver to chronic hepatitis, but also during transition into HCC. (Hepatology 2000;32:711-720.)
ISSN:0270-9139
1527-3350
DOI:10.1053/jhep.2000.17705