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GELSOLIN MAY BE A KEY TO EARLIER DIAGNOSIS AND TREATMENT OF BREAST CANCER

BUFFALO, NY - Roswell Park Cancer Institute (RPCI) scientists have found that the level of gelsolin, a protein responsible for maintaining actin filaments that are needed for healthy cells, may be of diagnostic and therapeutic value for breast cancer.

Ongoing studies of gelsolin, a multifunctional, actin-binding protein, have shown that levels of gelsolin are decreased in a majority of human and rodent breast cancers studied. Further, research indicates that normal levels of gelsolin have a tumor suppressor function. RPCI research teams led by Bonnie Asch, PhD, Chair, Division of Experimental Pathology, have or will soon publish the results of a number of studies that determined what causes gelsolin levels to decrease.

In the May issue of Experimental Cell Research, Lawrence Mielnicki, PhD, and colleagues reported that the administration of trichostatin A (TSA), a drug that acts as a specific histone deacetylase inhibitor, increased gelsolin levels in human breast cancer cells and caused their death. This observation supports the role of gelsolin as a suppressor of human breast cancer.

"We were attempting to learn how gelsolin is regulated in human breast cancer cells. We were surprised that TSA caused breast cancer cells to stop growing and die within 48 to 60 hours," said Dr. Asch. "Because TSA did not harm normal breast cells during the treatment period, TSA is a potential therapy against breast cancer."

Yan Dong, MS, and colleagues reported in the International Journal of Cancer that they had determined the frequency of abnormal gelsolin levels in breast cancers.Their research found 80-100 percent of cancers caused by a viral, chemical or hormonal agent had reduced gelsolin levels. It is believed that gelsolin decreases as cells undergo the transition from precancer to cancer. Another cellular defect, increased levels of a mammary oncogene, cyclin D1, was detected as well.

"According to our data, decreased levels of gelsolin and increased levels of cyclin D1 were found in human and rodent breast cancers," continued Dr. Asch. "This finding may offer a future diagnostic test for early-stage breast cancer because these changes appear to occur just as the cells begin the transition to cancer."

In related research, Harold Asch, PhD, Department of Experimental Pathology, and Janet Winston, MD, Division of Pathology & Laboratory Medicine, have found that the earliest breast lesions to exhibit reduced levels of gelsolin are a subset of atypical ductal hyperplasias. Results of their study will be published later this summer in Breast Cancer Research and Treatment.

Future studies will test TSA for its effects on human breast cancer cells growing in mice. This is an essential step prior to clinical trials in humans. Other research will focus on learning more about the cause of the gelsolin and cyclin D1 defects and determining if atypical ductal hyperplasias with these two molecular changes are the lesions most likely to progress to cancer.

Roswell Park Cancer Institute, founded in 1898, is the nation's first and one of its largest cancer research, treatment and education centers, and is the only National Cancer Institute-designated comprehensive cancer center in Western New York.

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