Activation of cyclin-dependent kinases CDC2 and CDK2 in hepatocellular carcinoma.
BACKGROUND
The cyclin-dependent kinases (CDKs) CDC2 and CDK2 are key regulators of the cell cycle. The expression of the CDK alone does not necessary reflect their true activities because they are highly regulated by post-translational mechanisms. Human hepatocellular carcinoma (HCC) is one of the most common cancers in the world, but the kinase activities of CDKs in HCC have not been examined.


METHODS
Here we examined the protein expression and kinase activities associated with CDC2 and CDK2 in HCC and the corresponding non-tumorous liver tissues.


RESULTS
CDC2 and CDK2 are activated in HCC in over 70% and 80% of the cases, respectively, but have little correlation with clinical parameters and PCNA expression. Interestingly, PCNA was readily detectable in extracts from non-tumorous liver, but more than 60% of samples contain higher concentration of PCNA in HCC than the corresponding non-tumorous tissues. CDC2 and CDK2 are generally activated in the same HCC samples, but the extent of their activation varied significantly, suggesting that the pathways leading to the activation of CDC2 and CDK2 can be regulated independently. Both positive regulators of CDK activity like cyclins and CDKs, and negative regulators of CDK activity like p21(CIP1/WAF1) and Thr14/Tyr15 phosphorylation were up-regulated in HCC.


CONCLUSIONS
CDC2 and CDK2 are activated in HCC, and this may be due to a complex interplay between the level of the cyclin, CDK, CDK inhibitors, and inhibitory phosphorylation.
Li
Kay K W
KK
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
Ng
Irene O L
IO
Fan
S T
ST
Albrecht
Jeffrey H
JH
Yamashita
Katsumi
K
Poon
Randy Y C
RY
D016203:CDC2 Protein Kinase / Q000378:metabolism*; D042846:CDC2-CDC28 Kinases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases