Friday, May 22, 2015

The Role of Telomerase Activity in Urothelial Cancer

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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