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


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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.

Sobre autores

I. Bondarev

University of Hawaii Cancer Research Center at Manoa; St. Petersburg Institute of Bioregulation and Gerontology

Email: khavinson@gerontology.ru
Estados Unidos da América, Honolulu, Hawaii, 96813; St. Petersburg, 197110

V. Khavinson

St. Petersburg Institute of Bioregulation and Gerontology

Autor responsável pela correspondência
Email: khavinson@gerontology.ru
Rússia, St. Petersburg, 197110

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