|
Protein linked to certain
cancer cell's immortality
BOSTON -- March 6, 2001-- Researchers have
identified a protein that approximately 10 percent of tumor cells
may use to attain their immortal state. By blocking this molecule,
it may be possible to stop these cancer cells from proliferating.
The approach might also be used as part of
a two-pronged strategy to combat the remaining 90 percent of
tumors, the researchers say.
The research team led by Dr. David Sinclair
and Haim Cohen at Harvard Medical School published their findings
in today's online early edition of the Proceedings of the
National Academy of Sciences.
"This gives us a new drug target for
cancer," said Sinclair, in a prepared statement.
In their early stages, tumor cells can only
undergo a limited number of divisions. Eventually, a handful
of cells, or possibly only one, breaks through this barrier and
gains the power to proliferate without end, ultimately giving
rise to a malignant mass.
Scientists have long known that most tumor
cells become malignant by turning on a gene for telomerase, a
protein that makes the protective caps at each end of a chromosome.
These nubs-- or telomeres-- erode every time a normal cell divides
and it is their steady unraveling that causes a cell to age and
die.
"The malignant cancer (cell) is generally
the one that revives its ability to make telomeres," said
Sinclair, assistant professor of pathology.
But a minority-- about 10 percent-- of cancer
cells manage to rebuild their telomeres without turning on the
telomerase gene. Sinclair and his colleagues have evidence that
they may be doing this by coopting a protein called, WRN, which
is thought to stabilize telomeres, though not actually build
them.
The researchers found that special yeast cells,
when deprived of their version of WRN, did not survive beyond
the normal number of cell divisions. Yeast cell colonies endowed
with their version of WRN, called SGS1, were able to proliferate
endlessly, presumably because one or a few yeast cells had found
a way to break through the barrier.
"In general, we can think of SGS1, and
the WRN protein, as longevity molecules," Sinclair said.
"Cancer cells may utilize the WRN protein for their own
purposes to become immortal and get around the barrier to tumorigenesis
and cancer formation."
If WRN plays the same role in the minority
of human cancer cells that survive without turning on telomerase,
the discovery could lead to a new tumor-fighting strategy.
"If we could block or inhibit the WRN
protein in these 10 percent of cancers, we'd have a good chance
of preventing proliferation," said Sinclair. Indeed, the
approach might even be applied to the 90 percent that attain
their immortality by switching on the telomerase gene. Researchers
have found that when they block the telomerase gene in those
cancer cells, some of the cells still manage to preserve telomeres,
presumably by switching to the WRN path.
"If you try and tackle the other 90 percent
by blocking their telomerase, they'll just jump into the other
pathway," Sinclair said. "So we have to have a double-pronged
attack."
Nature may have conducted a kind of clinical
trial of the anti-WRN strategy. People with a rare disease, Werner's
syndrome, are born without the WRN gene. While they age much
faster than other people, they do not develop common types of
cancers but instead are more likely to develop rarer cancers
such as sarcomas (muscle cancers) and meningiomas (brain tumors).
"It is possible that the absence of WRN
may give them partial protection, which is why these patients
don't develop these other more common cancers. This is pure speculation
at the moment," he said.
|