CURRENT RESEARCH INTO TELOMERES II
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Mon Aug 31 18:23:50 EST 1998
III. CURRENT RESEARCH INTO TELOMERES
B) TELOMERES, TELOMERASE AND CANCER
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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