Correlation of Telomerase Activity, hTERT mRNA Expression and HPV E6 Detection in Cervical Cancer Tissue

Hong, Jong Woo; Lee, Seon Kyung; Ban, Tae Hak; Ji, Sung Gil

Abstract

OBJECTIVE
Telomerase is a ribonucleoprotein enzyme which stabilizes chromosomal structure, thereby inducing cellular immortality. We investigated telomerase activity and human telomerase reverse transcriptase (hTERT) mRNA expression in relation to high-risk human papillomavirus (HPV) DNA presence in cervical carcinomas.
METHODS
From December 1995 to December 1999, at the department of obstetrics and Gynecology of Kyung-Hee University Hospital, 32 cervical carcinomas and 5 corresponding nontumor cervical tissues were obtained and the samples were immediately frozen and stored at -70 degree C. Telomerase activity was measured by using telomerase PCR ELISA, a modified version of the TRAP. Analysis of the expression of hTERT mRNA was performed by quantitative RT-PCR and the analysis of the HPV E6 gene was performed by DNA-PCR. RESULT: All of the carcinomas examined exhibited strongly positive for telomerase activity (OD>0.24), whereas telomerase activity was week or not found in the 5 corresponding nontumor cervical tissues. Quantitative RT-PCR analysis demonstrated significantly increased hTERT mRNA expression levels (>0.024) in most carcinomas comparing to control groups. There was no obvious relationship between telomerase activity levels and the clinical parameters examined including age, clinical stage, pathology, differentiation, tumour size, LN involvement and invasion depth except lymphovascular space invasion (p=0.03). In the correlation between the levels of hTERT mRNA expression and telomerase activity, correlation index which was 0.916, shows high correlation (p=0.01). According to the analysis of HPV E6 gene, 29 of 32 (90.6%) carcinomas showed HPV E6 positivity.
CONCLUSION
There is a strong association between telomerase activity and hTERT mRNA expression, and up-regulation of hTERT probably plays a role in the progression of cervical carcinomas. Telomerase is at least partially activated by viral oncogenes of high-risk types. There is no obvious relationship between telomerase activity levels and the clinical parameters except LSVI (p=0.03). These findings provides that telomerase may play an important role in the early stage of carcinogenesis.