Getting telomerase into normal cells (was Telomerase activity in "immortal" fish. (FWD))

T. Benjamin Csoka csoka at ITSA.UCSF.EDU
Thu Sep 24 16:09:21 EST 1998


Mike Sherrell wrote:


> Fine; how do we get telomerase into our cells?
>

Since the gene is already there in every cell, and is not mutated
(except, perhaps, in progeria ?), the better way would be to try to
activate the gene rather than replace it. Somebody ought to be looking
at the promoter and enhancer regions of the telomerase catalytic subunit
gene and looking for transcription factor binding sites etc. The
methylation status of the gene could also be investigated. Of course, we
do not yet have the technology to turn genes on and off at will even
with this knowledge, but it will come. For example it was recently shown
that mcy can turn on telomerase (see below).



> Genes Dev 1998 Jun 15;12(12):1769-1774
>
> Myc activates telomerase.
>
> Wang J, Xie LY, Allan S, Beach D, Hannon GJ
>
> Cold Spring Harbor Laboratory (CSHL), Cold Spring Harbor, New York 11724, USA.
>
> Telomere maintenance has been proposed as an essential prerequisite to human tumor development. The telomerase enzyme is itself a marker for
> tumor cells, but the genetic alterations that activate the enzyme during neoplastic transformation have remained a mystery. Here, we show that
> Myc induces telomerase in both normal human mammary epithelial cells (HMECs) and normal human diploid fibroblasts. Myc increases
> expression of hEST2 (hTRT/TP2), the limiting subunit of telomerase, and both Myc and hEST2 can extend the life span of HMECs. The ability
> of Myc to activate telomerase may contribute to its ability to promote tumor formation.
>


T. Benjamin Csoka





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