Telomerase, a ribonucleoprotein complex responsible for the maintenance of telomeres, is significantly expressed in 90% of cancer cells and apparently absent in normal somatic cells. Expression of the catalytic protein component of this telomerase complex, hTERT (human Telomerase Reverse Transcriptase), seems to be the limiting factor for telomerase activity, and plays a fundamental role in cellular immortalisation. Moreover, increasing observations indicate that hTERT protein could also have an anti-apoptotic function, independently from its role in telomere elongation.
The knowledge of the factors and mechanisms controlling hTERT expression would be highly significant to understand the telomerase re-activation process, a key step during immortalisation and onco-genesis in human cancers. At this date, few transcriptional factors are known to bind hTERT promoter but their actual contribution in telomerase regulation are not demonstrated. Moreover, published data from different laboratories indicate that important relevant transcription factors have not yet been identified.
Thus, the factors and mechanisms controlling the hTERT transcription still remain to be elucidated during physiological processes. Using our unique cellular model, in which telomerase can be regulated by several means by a physiological agent, all-trans retinoic acid, we propose to use a cDNA microarray approach to identify and select genes that could be specifically involved in hTERT regulation. In continuation, we will use a functional genomics approach to assess their actual contribution in that process. Our experiments would contribute to a better understanding of hTERT regulation mechanisms, and could also be important for the identification of new target genes for anti-cancer therapy.
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