Telomerase activity correlates with cell cycle regulators in human hepatocellular carcinoma.
OBJECTIVE
Mutation in cell cycle genes is the most common genetic change in malignant tumor cells. Telomerase activation, considered as essential in the immortality of cancer cells, is found in most cancers, where there may be an association with an active cell cycle.


METHODS
In this study study we used the TRAP assay to determine telomerase activity in liver tumor specimens from 25 cases of hepatocellular carcinoma (HCCs) as well as in corresponding non-cancerous liver tissue in each patient. The expression of cyclin D1, cdk2, and cdk4 protein was also examined by Western blot.


RESULTS
Twenty-one of the 25 cases of HCC were found to have increased telomerase activity, whereas only five out of the 25 non-cancerous liver samples were found to have weak telomerase activity. Telomerase activity was not found to be related to tumor size, HBsAg, HBeAg, anti-HCV, transaminase, or alpha-fetoprotein serum titer. Furthermore, three out of the 25 cases of HCC showed cyclin D1 overexpression, whereas 15 of the 23 cases of HCC showed decreased cyclin D1 expression. Down regulation of cyclin D1, cdk2, cdk4 protein correlated with telomerase activity (p<0.004, p<0.013, and p<0.001 respectively).


CONCLUSIONS
The results indicate that genetic defects in HCC facilitate the reactivation of telomerase activity, a process which may be dependent on cyclin D1 with its cyclin dependent kinase (cdk) partner defect.
Hsieh
H F
HF
Department of Surgery, Armed Force Taoyuan General Hospital, Taiwan.
Harn
H J
HJ
Chiu
S C
SC
Liu
Y C
YC
Lui
W Y
WY
Ho
L I
LI
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D021141:Nucleic Acid Amplification Techniques; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D019098:Telomerase / Q000378:metabolism*
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D019098:Telomerase