Suppression of alternative telomere lengthening in cancer cells with reverse transcriptase inhibitors
- Autores: Bondarev I.E.1,2, Khavinson V.K.2
-
Afiliações:
- University of Hawaii Cancer Research Center at Manoa
- St. Petersburg Institute of Bioregulation and Gerontology
- Edição: Volume 6, Nº 4 (2016)
- Páginas: 272-274
- Seção: Article
- URL: https://journals.rcsi.science/2079-0570/article/view/205057
- DOI: https://doi.org/10.1134/S2079057016040020
- ID: 205057
Citar
Resumo
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
Arquivos suplementares
