Researchers discover breast cancer gene inhibitor

After years of study, protein is found that blocks activity of HER-2 gene

Portland, Ore.-- Researchers at Oregon Health Sciences University and the Vollum Institute have discovered a naturally occurring protein that inhibits the functions of the HER-2 oncogene, a major factor in breast and other cancers. The protein, dubbed herstatin, blocks the HER-2 signaling activity that causes tumor cells to grow, ultimately killing those cells. The findings are reported in the September issue of Proceedings of the National Academy of Sciences.

"This particular gene, HER-2, has such a clear-cut role in breast cancer that if you can inhibit its biochemical activity, you should be able to control the cancer," said Gail Clinton, Ph.D., associate professor of biochemistry and molecular biology at OHSU's School of Medicine.

Clinton and her former student, Joni Doherty, M.D., Ph.D., discovered herstatin while investigating the reasons why HER-2 acts so aggressively in tumor development. An overabundance of HER-2 is present in 25 to 30 percent of breast cancer cases and results in significantly lower survival rates and shorter time to relapse. Besides breast cancer, HER-2 is strongly linked to ovarian, gastric, endometrial and salivary gland cancers and possibly to prostate and colon cancers.

Although the HER-2 oncogene was discovered nearly 20 years ago, and has been studied intensely by scientists around the world, herstatin is the first naturally occurring molecule found to inhibit HER-2. During their research, Clinton and Doherty uncovered a novel mechanism for generation of a HER-2 binding protein resulting in the discovery of herstatin. Because their work involved human cells in culture, there is promise that the protein can be developed into a treatment.

"It's a long way from cells in culture to treating patients, but we are very optimistic about our findings," Clinton said. In addition to Doherty, who is now a surgical fellow at the University of Southern California, other researchers involved were John Adelman, Ph.D., and Chris Bond, M.S., of the Vollum Institute and Armando Jardim, Ph.D., of OHSU.