Reactivation of telomerase in cancer

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• 作者：Semih Can Akincilar ; Bilal Unal ; Vinay Tergaonkar
• 关键词：TERT reactivation ; NF ; κB ; Tert promoter mutation ; Transcription ; Cancer
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：73
• 期：8
• 页码：1659-1670
• 全文大小：644 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biomedicine
  Life Sciences
  Biochemistry
  
• 出版者：Birkh盲user Basel
• ISSN：1420-9071

文摘

Activation of telomerase is a critical step in the development of about 85 % of human cancers. Levels of Tert, which encodes the reverse transcriptase subunit of telomerase, are limiting in normal somatic cells. Tert is subjected to transcriptional, post-transcriptional and epigenetic regulation, but the precise mechanism of how telomerase is re-activated in cancer cells is poorly understood. Reactivation of the Tert promoter involves multiple changes which evolve during cancer progression including mutations and chromosomal re-arrangements. Newly described non-coding mutations in the Tert promoter region of many cancer cells (19 %) in two key positions, C250T and C228T, have added another layer of complexity to telomerase reactivation. These mutations create novel consensus sequences for transcription factors which can enhance Tert expression. In this review, we will discuss gene structure and function of Tert and provide insights into the mechanisms of Tert reactivation in cancers, highlighting the contribution of recently identified Tert promoter mutations.