HTERT IS A CRITICAL DETERMINANT OF TELOMERASE ACTIVITY IN RENAL-CELL CARCINOMA

Telomerase is a ribonucleoprotein enzyme which stabilizes chromosomal structure, thereby inducing cellular immortality. Three major subunits composing telomerase complex have been cloned, designated hTR (human telomerase RNA), TPI (telomerase-associated protein I), and hTERT (hum an telomerase reverse transcriptase). In the present study, a total of 36 renal-cell carcinomas(RCC) and adjacent normal tissues, as well as cell lines derived from RCC or normal kidney, were examined for the e xpression of each telomerase subunit and telomerase activity. RT-PCR a nalyses revealed that hTR and TPI mRNA were constitutively expressed b oth in tumor and in normal tissues. In contrast, hTERT mRNA was expres sed in most tumors, but not in normal tissues. Telomeric-repeat-amplif ication-protocol (TRAP) assay revealed that more than 80% of RCC tumor tissue exhibited telomerase activity, while none of the adjacent norm al tissue did. There was a significant association of telomerase activ ity with expression of hTERT mRNA, but not with TP I mRNA or hTR expre ssion. Two cell lines, derived from RCC and cervical cancer, expressed telomerase activity and hTERT mRNA, while normal renal cortical epith elial cells expressed neither of them. These findings suggest that hTE RT plays a critical role in determining the enzymatic activity of huma n telomerase, and that up-regulation of hTERT probably plays a role in the progression of human cancers. (C) 1998 Wiley-Liss, Inc.