Suppression of alternative telomere lengthening in cancer cells with reverse transcriptase inhibitors
Autor: | V. Kh. Khavinson, I. E. Bondarev |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Telomerase Cancer Cell cycle Biology medicine.disease Molecular biology Reverse transcriptase Telomere 03 medical and health sciences Telomerase RNA component 030104 developmental biology 0302 clinical medicine Cancer cell Cancer research medicine Telomerase reverse transcriptase Geriatrics and Gerontology Gerontology 030217 neurology & neurosurgery |
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 |
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