May 11, 2009
UNC study identifies genetic cause of most common form of breast cancer
The discovery of tumor-suppressor genes has been key to unlocking
the molecular and cellular mechanisms leading to uncontrolled cell
proliferation – the hallmark of cancer. Often, these genes will work in
concert with others in a complex biochemical system that keeps our
cells growing and dividing, disease free.
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 the rest, eventually leading to
cancer.
This discovery, combined with new laboratory
techniques, will help scientists identify and test new treatments for
luminal-type tumors, which account for between 70 and 80 percent of all
breast cancers, but are generally slower growing than other types.
The results of the research appear in the May 2009 issue of Cancer Cell.
Defects
in the p18 gene have been observed in different types of human cancer.
Senior study author Yue Xiong, Ph.D., William R. Kenan Jr.
Distinguished Professor of biochemistry and biophysics, observes, "When
this gene is not expressed or is deleted, cells have no braking
mechanism. They will continue to grow and divide until they turn into
cancer."
Xiong and his colleagues specifically targeted the
role that p18 plays in the development of luminal breast cancers. Using
genetically-engineered mice with deletion of p18 genes, they created a
highly reliable model of human breast cancers. The researchers tested
their model by analyzing the gene in samples from approximately 300
human breast cancer patients, proving that the decreased expression of
the p18 gene is highly correlated with the development of luminal
tumors.
"The mechanism behind these tumors is quite different
from that of other forms of breast cancer. Understanding this mechanism
and having a good mouse model allows us to specifically test how
treatments work against these tumors, which may then benefit human
patients," said Xiong.
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.
School of Medicine contact: Les Lang, (919) 966-9366, llang@med.unc.edu
Lineberger center contact: Dianne Shaw, (919) 966-7834, dgs@med.unc.edu
Contact: Les Lang
llang@med.unc.edu
919-966-9366
SOURCE:
University of North Carolina School of Medicine
