Possible new drug still is three to five years
away.
Researchers at University of Utah's Huntsman Cancer
Institute have discovered a new target for possible future colon
cancer treatments – a molecule that is implicated in 85 percent of
colon cancer cases.
These findings were published online Oct. 6, 2006,
in the Journal of Biological Chemistry.
By knocking out - that is, genetically disabling -
a molecule called C-Terminal Binding Protein (CTBP) researchers were
able to rescue zebrafish from the effects of a mutation in the
adenomatous polyposis coli (APC) gene.
In humans, mutations in this gene long have been
known to initiate a series of events that cause colon polyps, which
eventually become cancerous. APC mutations play a role in 85 percent
of colon cancers. The new findings mean CTBP also is involved in that
proportion of colon cancers.
In zebrafish, APC mutations keep the intestine from
developing properly. "In essence, knocking out CTPB promotes normal
development of the intestine in zebrafish carrying an APC mutation,"
says David A. Jones, a University of Utah associate professor of
oncological sciences and leader of the study.
In normal cells of both humans and zebrafish, the
APC gene controls the amount of CTBP present by marking it for
destruction. In tumor cells with mutated APC, CTPB is not destroyed;
instead it accumulates in the cell.
One function of CTBP is to turn off the process
that converts vitamin A into retinoic acid in the cell. Retinoic acid
is essential in cell differentiation – the function that determines
what type of cell forms and how long it lives. This study observed
that in both zebrafish and human tissues with APC mutations, there are
high CTBP levels and low capability to produce retinoic acid. In
APC-mutated tissues in which CTBP had been "knocked out," retinoic
acid production was restored.
Earlier studies in Jones' lab showed that lack of
retinoic acid caused zebrafish intestines to form incorrectly, and
that adding retinoic acid corrected the problems.
"Knocking out CTBP does exactly the same thing, and
the logical conclusion is that it's because CTBP controls retinoic
acid production," says Jones. "Since CTBP is a completely new target,
we must now look for potential chemical agents that would work to
block its actions. That could take three to five years."
Colorectal cancer is the second leading cause
of cancer deaths in the United States. In 2006, the American
Cancer Society estimates that 106,680 cases of colorectal cancer
will be diagnosed in the nation, with 700 cases in Utah.
Colorectal cancer is the third most common cancer in the United
States and Utah.
-
Huntsman Cancer Institute's mission is to understand cancer
from its beginnings, to use that knowledge in the creation and
improvement of cancer treatments, to relieve the suffering of
cancer patients, and to provide education about cancer risk,
prevention, and care. HCI is a National Cancer
Institute-designated cancer center, which means that it meets the
highest national standards for cancer care and research and
receives support for its scientific endeavors. HCI is also a
member of the National Comprehensive Cancer Network, a nonprofit
alliance of the world's leading cancer centers, dedicated to
improving the quality and effectiveness of care provided to
patients with cancer.
ChemLin offers different
instruments with which you can publish or refer to the appropriate web
pages, press releases, product news, appointments etc.
For your personal publication please use this form.
