The telomerase activity and expression of hTERT gene can serve as indicators in the anti-cancer treatment of human ovarian cancer.
OBJECTIVE
The aim of this study was to evaluate the clinicopathological significance of telomerase activity and expression of hTERT gene in human ovarian cancer. The potential value of them as indicators for chemotherapy in ovarian cancer cells was also studied.


METHODS
A total of 73 samples and ovarian cancer cell lines HO-8910 and COC1 were studied. Telomerase activity was detected by PCR-TRAP-ELISA assay and the expression of the hTERT mRNA was analyzed by semi-quantitative RT-PCR. Alteration of the telomerase activity and hTERT mRNA were also analyzed in the ovarian cancer cells treated with different concentration and different time of cisplatin. Cytogenetic analysis was performed to compare the telomere status in the OH-8910 cells pre- and post-cisplatin treatment. The associations between these two markers and cisplatin induced-apoptosis were respectively analyzed in COC1 cells by the flow cytometry.


RESULTS
Telomerase activity are highly increased in malignancy (0.795+/-0.168(A450-655 nm)) than borderline (0.389+/-0.174(A450-655 nm)), benign tumors (0.236+/-0.102(A450-655 nm)) and normal ovary (0.213+/-0.070(A450-655 nm)) (p < 0.05). Twenty samples showed detectable levels of hTERT. The hTERT gene positive lesion showed significantly higher telomerase activity than negative (p = 0.004). There is a significant correlation between the telomerase activity and expression of hTERT (r = 0.921). Both telomerase activity and expression of hTERT can reflect the chemotherapeutic effect of cisplatin in a time-dependent and dose-dependent manner. Treatment with 10 microM cisplatin, the hTERT mRNA decreased after 12h and completely disappeared after 48 h, whereas the telomerase activity did not decrease until 24h. Results from cytogenetic analysis and flow cytometry assay confirmed that the alterations of these two markers are associated with the anti-cancer treatment of cisplatin.


CONCLUSIONS
Expression of hTERT gene is rate-limiting with the activation of telomerase. Both of they may be useful in the predicting of chemotherapeutic effect in ovarian cancer.
Sun
Peng-Ming
PM
Department of Obstetrics and Gynecology, Peking University People's Hospital, Peking University Health Science Center, Xizhimen South Street No. 11, 100044 Beijing, PR China. dr.sunfengming@gmail.com
Wei
Li-Hui
LH
Luo
Mei-Yu
MY
Liu
Guang
G
Wang
Jiang-Liu
JL
Mustea
Alexander
A
Könsgen
Dominique
D
Lichtenegger
Werner
W
Sehouli
Jaild
J
D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D010053:Ovary / Q000378:metabolism*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis*; D019098:Telomerase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase; D002945:Cisplatin