UNC Study Identifies Genetic Cause Of Most Common Form Of Breast Cancer
NewsRx.com
June 18, 2009
Cancer is a disease of runaway cell proliferation. Normally, a variety of genes coordinate to keep cell growth under control and on track. If a gene goes awry at any step in the cell cycle, another can compensate to keep cancer from developing.
Now researchers at the University of North Carolina at Chapel Hill School of Medicine and UNC Lineberger Comprehensive Cancer Center have found that defects in one gene called p18 may override all the rest, eventually leading to breast cancer.
The results of the research appear in the May 2009, issue of Cancer Cell. The study also reports a new mouse model -- lacking p18 -- that can help scientists identify and test new treatments for the most common type of breast cancer.
"This gene is an inhibitor of cell proliferation essentially, it is the brakes that keeps the cell from growing out of control," said senior study author Yue Xiong, Ph.D., William R. Kenan Jr. Distinguished Professor of biochemistry and biophysics and a Lineberger member. "If the brakes aren't working, the cell will not be able to stop when it needs to and instead will continue to grow and divide until it turns into cancer."
Defects in the p18 gene have been observed in different types of human cancer. Xiong and his colleagues looked specifically at the role this gene plays in the development of breast cancer. They genetically engineered mice to be defective in p18 and found that the mutant mice developed mammary tumors at a rate of nearly 90 percent, far superior to other mutants currently used for cancer research. Furthermore, the mammary tumors that arose in these mice mimic the form of breast cancer luminal-type that accounts for 70 to 80 percent of cases in humans.
"We know that tumors are not all equal," Xiong said. "For luminal-type tumors, their prognosis, pathogenesis, treatment and response are quite different from that of the other form, basal-type tumors. To understand how the luminal-type tumor develops is critically important, not only for understanding the process but more importantly how we can treat them in the future. Having a good mouse model that develops tumors of one type or another allows us to specifically test how treatments work against a specific tumor type that may then benefit human patients."
To determine whether their mice truly model human disease, the researchers analyzed the gene in samples from approximately 300 breast cancer patients. They discovered that loss of the p18 gene correlates with the development of luminal-type tumors in humans as well as mice.
Xiong and his colleagues are now using this model to understand how the breast cancer types differ. They are particularly interested in investigating differences between the luminal-type tumors caused by defects in p18 and basal-type tumors caused by defects in the BRCA1 breast cancer gene. The researchers are currently creating a mouse model that contains mutations in both genes to explore why different genetic defects lead to different types of breast cancer.
The research was supported by the National Cancer Institute Breast SPORE program, the National Institutes of Health and the Breast Cancer Research Foundation.
Study co-authors from the UNC Lineberger Comprehensive Cancer Center include Xin-Hai Pei, Ph.D., research assistant professor; Feng Bai, M.D., Ph.D., research associate; Matthew D. Smith, research specialist; Jerry Usary, research associate; Cheng Fan, research associate; and Charles M. Perou, Ph.D., associate professor of genetics and pathology and laboratory medicine.
Copyright 2009, Genetics & Environmental Law Weekly via NewsRx.com
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