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Compounds Block ras Gene Function Compounds Block ras Gene Function

Compounds Block ras Gene Function Compounds Block ras Gene Function

TORONTO, Canada--For years, scientists have known that defective
genes allow tumors to grow. Today, researchers blame as many as
30% of all cancers on just one of those genes, the ras
gene, the first oncogene discovered in human cancers. Animal research
presented at the meeting of the American Association for Cancer
Research (AACR) may someday lead to cancer drugs that can block
the effects of this oncogene in humans.

The ras gene plays a pivotal role in cell biology, Saïd M.
Sebti, PhD, said at a media conference held in conjunction with
the AACR meeting. The gene acts as a controller--a dispatcher
that passes on biochemical signals to cells. The signals, in the
form of proteins, tell the cell when to divide and when to stop

Scientists believe that when the normal form of the ras gene is
somehow damaged, whether through exposure to a carcinogen such
as cigarette smoke or through a spontaneous biochemical mistake
when the cell replicates, the protein ultimately manufactured
by the defective, mutated form of the ras gene is a permanently
switched-on protein that defies signals to stop cell growth. The
result is continuous, unstoppable cell division and tumor enlargement.

Dr. Sebti, associate professor of pharmacology, University of
Pittsburgh, said that his team, in collaboration with the team
of his colleague Andrew D. Hamilton, PhD, professor of chemistry,
has successfully designed and tested in mice a new class of compounds
that selectively block the function of the mutant ras gene.

He noted that the ras protein has to become hooked to the
underside of the cell membrane. If it does not become anchored
in this way, the mutant ras protein stays in the cell's
interior and stops functioning, so there is no rampant cell division.

The University of Pittsburgh researchers found that nonpeptide
peptidomimetics can be used to selectively block mutant ras
gene activity. These agents mimic peptides in the way that they
interact with farnesyl transferase, the enzyme that helps the
ras protein attach to the cell membrane, Dr. Sebti said.

Nontoxic to Normal Cells


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