Cyclins and cyclin-dependent kinases: comparative study of hepatocellular carcinoma versus cirrhosis. Export

@article{citeulike:762646, abstract = {Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kinase activity levels between hepatitis C virus (HCV)-induced HCC and HCV-induced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1-related kinase activity in HCC was accompanied by the up-regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC.}, address = {Third Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan. tmasaki@kms.ac.jp}, author = {Masaki, T. and Shiratori, Y. and Rengifo, W. and Igarashi, K. and Yamagata, M. and Kurokohchi, K. and Uchida, N. and Miyauchi, Y. and Yoshiji, H. and Watanabe, S. and Omata, M. and Kuriyama, S.}, citeulike-article-id = {762646}, citeulike-linkout-0 = {http://dx.doi.org/10.1053/jhep.2003.50112}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12601350}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12601350}, doi = {10.1053/jhep.2003.50112}, issn = {0270-9139}, journal = {Hepatology}, keywords = {cell-cycle, hepatocellular}, month = {March}, number = {3}, pages = {534--543}, posted-at = {2006-07-18 01:41:12}, priority = {2}, title = {Cyclins and cyclin-dependent kinases: comparative study of hepatocellular carcinoma versus cirrhosis.}, url = {http://dx.doi.org/10.1053/jhep.2003.50112}, volume = {37}, year = {2003} }

TY - JOUR ID - citeulike:762646 L3 - citeulike-article-id:762646 N2 - Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kinase activity levels between hepatitis C virus (HCV)-induced HCC and HCV-induced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1-related kinase activity in HCC was accompanied by the up-regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC. IS - 3 JF - Hepatology SN - 0270-9139 AD - Third Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan. tmasaki@kms.ac.jp EP - 543 TI - Cyclins and cyclin-dependent kinases: comparative study of hepatocellular carcinoma versus cirrhosis. VL - 37 SP - 534 KW - cell-cycle KW - hepatocellular AU - Masaki, T AU - Shiratori, Y AU - Rengifo, W AU - Igarashi, K AU - Yamagata, M AU - Kurokohchi, K AU - Uchida, N AU - Miyauchi, Y AU - Yoshiji, H AU - Watanabe, S AU - Omata, M AU - Kuriyama, S PY - 2003/03// UR - http://dx.doi.org/10.1053/jhep.2003.50112 ER -