Telomerase is an enzyme whose activity within a cell leads
to cell immortality due to repeated cell divisions. The telomerase enzyme is highly active in
embryonic cells and in stem cells where uninterrupted cell divisions are
requisite for the role of these cells in the growth and development of the
individual organism. In addition, telomerase activity is a
significant factor in cancer – its activity has been shown to be up-regulated
in over 85% of cancers. However, there
is no detectable telomerase activity in most somatic – body – cells. This lack of activity is due to the suppressed
production of telomerase reverse transcriptase (TERT). It has been suggested that mutations
associated with TERT reactivation may be the, “most prevalent of all noncoding
mutations in cancer.”
The question, of course, arises as to what is the cellular
event that turns on telomerase activity in cancerous cells. Due to exhaustive genetic analysis, there is
evidence of point mutations in the TERT gene promoter in many cancer types
including urothelial cancer (UC) – UC ranks five in the number of cancer cases
reported in the Western world. However,
it remained unclear as to whether any of these mutations actually results in
the reactivation of telomerase.
Dr. Sumit Borah from Howard Hughes Medical Institute at the
University of Colorado BioFrontiers Institute in Boulder Colorado and collaborators
from other institutions have done genetic studies on cell lines from 23
different UC patients. They have clearly
shown a correlation between these mutations and higher levels of TERT messenger
– mRNA -, TERT protein and, most importantly, telomerase enzymatic activity. Furthermore this group of investigators has
established that elevated levels of TERT m-RNA expression is strongly
associated with reduced survival in two independent UC patient studies.
These findings are highly significant; because they further elucidate
the underlying genetic mechanisms that can transform a normal cell into a
cancerous one.
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