Bondarev I E, Khavinson V Kh
University of Hawaii Cancer Research Center at Manoa, Honolulu, Hawaii, 96813 USA.
Saint-Petersburg Institute of Bioregulation and Gerontology, Saint-Petersburg, 197110, Russian Federation;
Adv Gerontol. 2016;29(2):218-221.
Telomerase is a ribonucleoprotein enzyme that elongates telomeres and therefore maintains chromosomal stability in germline, and 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 authors show that human tumor-derived ALT cell lines express a LINE-1 (L1) retrotransposon, which suggests its participation in telomere maintenance, possibly by a «slippage» mechanism of telomeric DNA synthesis. Moreover, suppression of the L1 encoded reverse transcriptase activity using an antisense strategy, or treatment of the ALT cells with the reverse transcriptase inhibitor 3'-azido-2',3'-dideoxythymidine (AZT), induces progressive telomere loss, arrest in G2-phase of the cell cycle, and, eventually, in cancer cell death. This finding suggests an exciting opportunity for the cure of up to 30 % of cancer cases.
端粒酶是一种核糖核蛋白酶，可延长端粒，从而在细胞倍增过程中维持生殖系以及大多数癌细胞中的染色体稳定性。然而，高达30%的不同类型人类肿瘤不表达端粒酶，而是采用端粒替代延长（ALT）机制。本文作者表明，源自人类肿瘤的ALT细胞系表达一种LINE-1（L1）逆转录转座子，这表明其可能通过端粒DNA合成的“滑动”机制参与端粒维持。此外，使用反义策略抑制L1编码的逆转录酶活性，或用逆转录酶抑制剂3'-叠氮基-2'，3'-双脱氧胸苷（AZT）处理ALT细胞，会导致端粒逐渐丢失、细胞周期停滞于G2期，并最终导致癌细胞死亡。这一发现为治愈高达30%的癌症病例提供了一个令人振奋的机会。
