(Ivanhoe Newswire) -- Researchers have been able to show in mice how just
a little adjustment in the expression of two common genes can promote the kinds
of cellular changes that lead to breast cancer. They say these changes probably
mimic natural variations women have in expression of the two genes.
Researchers at Georgetown Lombardi Comprehensive Cancer Center say that a
readout in healthy women of these two genes -- estrogen receptor alpha and p53 –
could provide an "interacting biomarker" that might predict future breast cancer
risk.
"It was believed that both of these genes only act once breast cancer had
developed – p53 mutations are found in many cancers, including breast cancer,
and the majority of women with breast cancer have over-expression of this common
estrogen receptor," lead investigator Priscilla A. Furth, M.D., a professor of
oncology and medicine at Georgetown University Medical Center, was quoted as
saying.
"What wasn't known is that different levels of expression of these genes can
help launch the cellular changes that lead to breast cancer," Dr. Furth said.
"That suggests that testing women for their own variations in these genes might
potentially give us a clue as to which women are at higher risk for development
of breast cancer."
One focus of Dr. Furth's lab is to eventually develop a panel of tests that will
accurately determine an individual woman's future risk of developing breast
cancer so that counseling and monitoring can be tailored to each patient. To
find the genes and proteins that carry such risks, she has developed mouse
models in which she can manipulate various genetic factors to see how breast
cancer risk changes over time.
First author Edgar S. Díaz-Cruz, Ph.D., fellow at Lombardi, and Dr. Furth
developed mice in which one copy of the p53 gene was silenced (mice, and humans,
inherit two copies, one from each parent), and tested the effect on development
of preneoplasia, or early breast cancer. The p53 gene, called the "guardian of
the genome," is a very powerful tumor suppressor that regulates cell growth.
Alterations to p53 are reported in 30 to 40 percent of human breast cancers, and
these changes are linked to increased cancer aggressiveness, poor prognosis and
chemotherapy resistance.
"Normal breast tissue functioning requires a balance of cell growth and cell
death, and in this study we found both deregulated estrogen receptor function
and p53 expression independently, and in combination, altering this balance and
transforming cells," Dr. Furth said.
Dr. Furth explained that both tweaks in gene expression levels were relatively
minor and said she was sobered to find that they had such a profound effect on
otherwise healthy breast tissue. "We increased ER expression, but in a way that
could be found in normal variation among women," she said. "And the mice lost
one of their two p53 genes, but loss of that single copy only decreases but does
not eliminate expression."
Dr. Furth concluded, "These are not the only two molecules that are responsible
for breast cancer development, but they are important and they can potentially
provide us with an early warning or even with prevention strategies."
SOURCE: Cancer Research, online, May 15, 2010
