EXPRESSION OF HUMAN TELOMERASE SUBUNITS AND CORRELATION WITH TELOMERASE ACTIVITY IN UROTHELIAL CANCER

The activation of telomerase and stabilization of telomeres are though t to be required for cellular immortality and oncogenesis. Three major components of human telomerase-human telomerase RNA (hTERC), telomera se-associated protein (TEP1), and human telomerase catalytic subunit ( hTERT)-have recently been identified. However, the roles played by the se subunits in the regulation of telomerase activity are still unclear . In the present study, a total of 37 urothelial cancers, including on e metastatic lesion, and adjacent normal tissues as well as cell lines derived from bladder cancers were examined for the expression of each telomerase subunit, Reverse transcription-PCR analysis revealed that more than 90% of urothelial cancers expressed hTERT mRNA, whereas less than 20% of normal adjacent tissues did. In contrast, hTERC and TEP1 mRNA were commonly expressed in both cancers and normal tissues, All o f the three cell lines derived from bladder cancer expressed each of t he telomerase subunits, whereas the two normal primary fibroblast cell lines expressed hTERC and TEP1 mRNA but not hTERT mRNA, Telomerase ac tivity was examined using telomeric repeat amplification protocol assa y. All of the cancers examined exhibited telomerase activity, whereas only 2 of 12 normal tissues exhibited weak activity. There was a signi ficant association of telomerase activity with hTERT mRNA expression b ut not with hTERC or TEP1 mRNA expression. These findings provide stro ng evidence that the expression of hTERT is a rate-limiting determinan t of the enzymatic activity of human telomerase and that the up-regula tion of hTERT expression may play a critical role in human carcinogene sis.