Genetics: Early Warning of Future Breast Cancer
Reported May 14, 2010
(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