Suppression of alternative telomere lengthening in cancer cells with reverse transcriptase inhibitors

Autor: V. Kh. Khavinson, I. E. Bondarev
Rok vydání: 2016
Předmět:
Zdroj: Advances in Gerontology. 6:272-274
ISSN: 2079-0589
2079-0570
DOI: 10.1134/s2079057016040020
Popis: Telomerase is a ribonucleoprotein enzyme that elongates telomeres and therefore maintains chromosomal stability in germ lines, as well as in the majority of cancer cells during cell doubling. However, up to 30% of human tumors of different types do not express telomerase but instead use an alternative lengthening of telomeres (ALT). Here we show that human tumor-derived ALT cell lines express a LINE-1 (L1) retrotransposon. This indicates its participation in telomere maintenance, possibly, by a slippage mechanism during telomeric DNA synthesis. Moreover, the suppression of L1-encoded reverse transcriptase activity by antisense strategy or treatment of ALT cells with reverse transcriptase inhibitor 3'-azido-2',3'-dideoxythymidine (AZT) induces progressive telomere shortening, arrest in G2 phase of the cell cycle, and, eventually, cancer cell death. This finding suggests a unique opportunity to cure cancer in a number of cases.
Databáze: OpenAIRE