Excelife excelife at
Mon Aug 31 18:23:50 EST 1998



The enzyme telomerase is a naturally occurring enzyme that helps to maintain 
telomeric length in various cells of the body, most noticeably the germ and 
stem cells.  In most other cells telomerase is active during embryonic 
development but is "shut off" when the cell terminally differentiates.

Telomerase has been shown to be active in the majority of cancers and its 
ability to add or maintain telomeric length on the chromosomes allows human 
cells to by-pass their senescent and crisis stages.  Telomeric maintenance or 
lengthening is also the most likely reason that cancer cells are immortal.

Research is being conducted to determine how and why telomerase is 
reactivated in senescent or crisis stage cells.  Some research is looking at 
the breakdown of the chromosome containing the gene for telomerase.  The 
breakdown of this chromosome could be the result of the loss of telomeric 
length.  The unregulated gene could then express the enzyme telomerase and 
once expressed it restabilizes the chromosomes by adding telomeres back to 
the chromosomes allowing them to replicate while still producing telomerase.

This is just one of the ways that a cell can become immortalized in cancers. 
The other genetic products expressed with the breakdown of the chromosome 
could cause the changes observed in cancerous tissues.  Most likely a 
combination of events is required to actually develop cancer but without the 
expression of telomerase, in most cases, the cancerous cells could not 
continue to proliferate. 

Geron Corp., as mentioned earlier, is investigating methods to inhibit the 
activity of telomerase in cancerous tissue.  But they are far from alone!
A medline search for telomerase and cancer turns up almost 500 hits.

Much of this research involves determining if the enzyme telomerase is 
present in particular types of cancer and it has been found to be active in 
approx. 95% of all cancers studied.

In the few cases where telomerase has not been detected, the cancerous cells 
still show elongated telomeres.  In these cases either the telomerase gene 
was expressed earlier, adding telomeric length to the chromosomes and then 
being "switched off" at a later time or there is an alternative process at 
work maintaining telomeric length.

Some research studies have identified alternative methods of maintaining 
telomeric length including specific genes that can add telomeres to 
chromosomes in the absence of telomerase, recombinant DNA processes that can 
help maintain telomeric stability and even free floating genetic material 
that codes for telomeric repeats.

While some of these alternative processes are part of the cells normal 
regulatory functions, their activation in senescent or crisis cells, like the 
inappropriate activation of telomerase, is an aberration and possibly the 
results of mutations to the genes, cellular damage from numerous sources or 
perhaps inherited genetic defects.

(next: Other Telomere Research) 

Thomas Mahoney, Pres.
Lifeline Laboratories, Inc. 

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