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

Telomerase activity is involved in the maintenance of telomere length and i s thought to be required for cellular immortality and oncogenesis. Three ma jor subunits composing telomerase, human telomerase RNA (hTR), telomerase-a ssociated protein (TPI) and human telomerase catalytic subunit (hTERT), hav e been identified. However, their functions and the regulatory mechanisms b y which telomerase is activated have not been fully determined. In the pres ent study, a total of 35 epithelial ovarian cancers, 5 ovarian low potentia l malignancies (LPM), 11 ovarian benign cysts and 12 normal ovaries, as wel l as various cell lines derived from ovarian cancers, were examined for the expression of hTR, TPI mRNA and hTERT mRNA. Correlations of expression wit h telomerase activity were evaluated. Reverse transcription-polymerase chai n 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. F ive telomerase-positive ovarian cancer cell lines expressed each of the tel omerase subunits, whereas 2 telomerase-negative normal primary fibroblast c ell lines expressed TPI mRNA and hTR, but not hTERT mRNA, There was a signi ficant correlation of telomerase activity with hTERT mRNA expression but no t with TPI or hTR expression. Expression of hTERT is thus specific to cance r lesions and appears to be a rate-limiting determinant of the enzymatic ac tivity of human telomerase. Up-regulation of hTERT may play a critically im portant role in the development of ovarian cancers. Int. J. Cancer 80:804-8 09, 1999. (C) 1999 Wiley-Liss, Inc.