Reducing Specific Gene Levels Makes Breast Cancer Cells More Responsive to Ionizing Radiation
ANAHEIM, CALIF. (April 20, 2005) -- Reducing expression of a gene called BRCC36 that interacts with the breast cancer susceptibility gene 1 (BRCA1) makes breast cancer cells more responsive to ionizing radiation, according to scientists at Fox Chase Cancer Center in Philadelphia. The research was presented today at the 96th Annual Meeting of the American Association for Cancer Research (AACR) in Anaheim, Calif.
BRCC36 directly interacts with the BRCA1 protein. Almost all invasive breast cancer cells have elevated BRCC36 levels compared to normal breast milk-duct cells.
"Since BRCC36 directly affects BRCA1 and BRCA1 is activated after exposure to radiation, we wanted to see if BRCC36 might be important in this response," said Xiaowei Chen, PhD, a Fox Chase postdoctoral researcher in the laboratory of geneticist Andrew K. Godwin, PhD, and the study's lead author.
Working with breast-cancer cell line MCF-7, the Fox Chase scientists reduced BRCC36 expression by 80 percent. They then exposed the cells to radiation, similar to that used in breast cancer treatment. They found that the number of breast cancer cells killed by the radiation increased by about 10 percent compared to cells that did not have their BRCC36 levels reduced.
"These findings hold promise for future breast cancer treatments," Chen said. "BRCC36 may be a target to manage radiation-resistant breast cancer cells. Our next step is to find out why the cells with reduced BRCC36 are more sensitive to radiation."
Along with Chen, study authors are Godwin and surgical fellow Cletus Arciero, M.D. The research is supported in part by the AACR Anna D. Barker Fellowship, the Eileen Stein-Jacoby Fund and a grant from the Department of Defense.
96th Annual Meeting of the American Association for Cancer Research
Poster Session: Radiation Biology 4
Exhibit Hall B-D, Anaheim Convention Center
Abstract #5701, Board #23:
Inhibition of BRCC36, a Novel Subunit of a BRCA1 E3 Ubiquitin Ligase Complex, Promotes Ionizing Radiation-Induced Apoptosis in Breast Cancer Cells
To be presented Wednesday, April 20, 2005, from 8 a.m. to 12 noon PT
Fox Chase Cancer Center, part of Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase also was among the first institutions to receive the National Cancer Institute’s prestigious comprehensive cancer center designation in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are routinely recognized in national rankings, and the Center’s nursing program has achieved Magnet status for excellence three consecutive times. Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research and oversees programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX-CHASE (1-888-369-2427).