Expression of human telomerase subunits in ovarian malignant, borderline and benign tumors

Abstract

Telomerase activity is involved in the maintenance of telomere length and is thought to be required for cellular immortality and oncogenesis. Three major subunits composing telomerase, human telomerase RNA (hTR), telomerase- associated protein (TPI) and human telomerase catalytic subunit (hTERT), have been identified. However, their functions and the regulatory mechanisms by which telomerase is activated have not been fully determined. In the present study, a total of 35 epithelial ovarian cancers, 5 ovarian low potential malignancies (LPM), 11 ovarian benign cysts and 12 normal ovaries, as well as various cell lines derived from ovarian cancers, were examined for the expression of hTR, TPI mRNA and hTERT mRNA. Correlations of expression with telomerase activity were evaluated. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that hTR and TPI mRNA were expressed in more than 80% of ovarian cancers, LPM, ovarian cysts and even in normal ovaries. However, hTERT mRNA was observed only in ovarian cancers, most of which exhibited telomerase activity. Normal ovarian tissues, ovarian cysts and LPM, most of which had no telomerase activity, did not express hTERT. Five telomerase-positive ovarian cancer cell lines expressed each of the telomerase subunits, whereas 2 telomerase-negative normal primary fibroblast cell lines expressed TPI mRNA and hTR, but not hTERT mRNA. There was a significant correlation of telomerase activity with hTERT mRNA expression but not with TPI or hTR expression. Expression of hTERT is thus specific to cancer lesions and appears to be a rate-limiting determinant of the enzymatic activity of human telomerase. Up-regulation of hTERT may play a critically important role in the development of ovarian cancers.