Advances in Gerontology

, Volume 6, Issue 4, pp 272–274 | Cite as

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

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Abstract

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.

Keywords

telomeres telomerase alternative lengthening of telomeres reverse transcriptase inhibitors 

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Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  1. 1.University of Hawaii Cancer Research Center at ManoaHonoluluUSA
  2. 2.St. Petersburg Institute of Bioregulation and GerontologySt. PetersburgRussia

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