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2016 ; 73
(8
): 1659-70
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Reactivation of telomerase in cancer
#MMPMID26846696
Akincilar SC
; Unal B
; Tergaonkar V
Cell Mol Life Sci
2016[Apr]; 73
(8
): 1659-70
PMID26846696
show ga
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.
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