Alternatively spliced variant deleting exons 7 and 8 of the human telomerase reverse transcriptase gene is dominantly expressed in the uterus

The expression level of the human telomerase reverse transcriptase (hTERT) is a rate-limiting determinant of telomerase activity. Several alternativel y spliced variants of hTERT transcript are currently known. We have studied the expression of the splicing variants arising in the transcript encoding the reverse transcriptase domain, and have compared this to the telomerase activity in 27 endometria, 14 myometria and 18 endometrial carcinomas. Tel omerase activity and the full-length hTERT transcript were observed in endo metrial samples from the proliferative and early secretory phases, but not in those from the late secretory phase. Steady-state expression of the hTER T splicing variant entirely lacking exon 7 and exon 8 was observed in the e ndometria throughout the menstrual cycle. In the analysed myometria, this t ype of splicing variant was the most commonly detected, and telomerase acti vity occurred in only three samples. In both endometria and myometria, the expression of the full-length transcript correlated well with the telomeras e activity. In each of the endometrial carcinomas, telomerase activity was detected and the full-length transcript was found together with varying com binations of deletion splicing variants. These results suggest that regulat ion of splicing in the transcript encoding the hTERT reverse transcriptase domain is associated with telomerase activation in uterine tissues.