North Carolina researchers identify genetic cause of breast cancer
Researchers at the University of North Carolina at Chapel Hill School of Medicine and UNC Lineberger Comprehensive Cancer Center have found that defects in a gene called p18 prevents tumor-suppressor genes from controlling healthy cell proliferation, leading to cancer. According to the researchers, their discovery may lead to new test treatments for luminal-type tumors, which account for between 70 and 80 percent of all breast cancers.
CHAPEL HILL, N.C.—Researchers at the University of North Carolina at Chapel Hill School of Medicine and UNC Lineberger Comprehensive Cancer Center have found that defects in a gene called p18 prevents tumor-suppressor genes from controlling healthy cell proliferation, leading to cancer. According to the researchers, their discovery may lead to new test treatments for luminal-type tumors, which account for between 70 and 80 percent of all breast cancers.
"This finding provides the direct evidence that defect in a cell cycle regulator leads to the exit of progenitor cells from their normal quisences state and enter into proliferation cycle, explaining how this group of genes, known as INK4 cell cycle inhibitors, suppress tumorigenesis," says Dr. Yue Xiong, a professor of biochemistry and biophysics at the Lineberger Cancer Center and senior author on the study.
The study, published in the May 2009 issue of Cancer Cell, explains that the p18 gene is an inhibitor of cell proliferation. Defects in p18 in mouse models are known to cause tumor development in several organs, including brain, endocrine organs, prostate, lung and lymphomas. Defects in p18 gene have also been observed in several type of human cancers, including brain tumor, lymphoma and endocrine organs.
Xiong and his team specifically targeted the role that p18 plays in the development of luminal breast cancers using genetically-engineered mice with deletion of p18 genes. 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 p18-deficient mice develop a particular type of mammary tumor, known as ER-positive luminal tumor, which account for majority of human breast cancer," Xiong says. "With this unique mouse strain in hand, we could use it to test the drugs for the treatment of human ER-positive luminal breast cancer."
The study was co-authored by Dr. Xin-Hai Pei, research assistant professor; Dr. Feng Bai, research associate; Matthew D. Smith, research specialist; Jerry Usary, research associate; Cheng Fan, research associate; and Dr. Charles M. Perou, associate professor of genetics and pathology and laboratory medicine. The research was funded by the National Cancer Institute Breast SPORE program, the National Institutes of Health and the Breast Cancer Research Foundation.
"This finding provides the direct evidence that defect in a cell cycle regulator leads to the exit of progenitor cells from their normal quisences state and enter into proliferation cycle, explaining how this group of genes, known as INK4 cell cycle inhibitors, suppress tumorigenesis," says Dr. Yue Xiong, a professor of biochemistry and biophysics at the Lineberger Cancer Center and senior author on the study.
The study, published in the May 2009 issue of Cancer Cell, explains that the p18 gene is an inhibitor of cell proliferation. Defects in p18 in mouse models are known to cause tumor development in several organs, including brain, endocrine organs, prostate, lung and lymphomas. Defects in p18 gene have also been observed in several type of human cancers, including brain tumor, lymphoma and endocrine organs.
Xiong and his team specifically targeted the role that p18 plays in the development of luminal breast cancers using genetically-engineered mice with deletion of p18 genes. 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 p18-deficient mice develop a particular type of mammary tumor, known as ER-positive luminal tumor, which account for majority of human breast cancer," Xiong says. "With this unique mouse strain in hand, we could use it to test the drugs for the treatment of human ER-positive luminal breast cancer."
The study was co-authored by Dr. Xin-Hai Pei, research assistant professor; Dr. Feng Bai, research associate; Matthew D. Smith, research specialist; Jerry Usary, research associate; Cheng Fan, research associate; and Dr. Charles M. Perou, associate professor of genetics and pathology and laboratory medicine. The research was funded by the National Cancer Institute Breast SPORE program, the National Institutes of Health and the Breast Cancer Research Foundation.
