Telomerase activity correlates with cell cycle regulators in human hepatocellular carcinoma

Aims/background: Mutation in cell cycle genes is the most common genetic ch ange in malignant tumor cells. Telomerase activation, considered as essenti al in the immortality of cancer cells, is found in most cancers, where ther e may be an association with an active cell cycle. Methods: In this study s tudy we used the TRAP assay to determine telomerase activity in liver tumor specimens from 25 cases of hepatocellular carcinoma (HCCs) as well as in c orresponding non-cancerous liver tissue in each patient. The expression of cyclin D1, cdk2, and cdk4 protein was also examined by Western blot. Result s: Twenty-one of the 25 cases of HCC were found to have increased telomeras e activity, whereas only five out of the 25 non-cancerous liver samples wer e found to have weak telomerase activity. Telomerase activity was not found to be related to tumor size, HBsAg, HBeAg, anti-HCV, transaminase, or alph a-fetoprotein serum titer. Furthermore, three out of the 25 cases of HCC sh owed cyclin D1 overexpression, whereas 15 of the 23 cases of HCC showed dec reased cyclin D1 expression. Down regulation of cyclin D1, cdk2, cdk4 prote in correlated with telomerase activity (p<0.004, p<0.013, and p<0.001 respe ctively). Conclusion: The results indicate that genetic defects in HCC faci litate the reactivation of telomerase activity, a process which may be depe ndent on cyclin D1 with its cyclin dependent kinase (cdk) partner defect.