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University of Iowa research shows how maspin gene suppresses breast cancer

IOWA CITY, Iowa -- A University of Iowa study is providing new insight into how the tumor suppressor gene maspin (mammary serine protease inhibitor) works.

The UI findings, included in the Dec. 15 issue of Cancer Research, may allow scientists to develop novel ways of treating breast cancer, said Mary J.C. Hendrix, Ph.D., UI professor and head of anatomy and cell biology, and associate director of basic research at the UI Cancer Center.

"This is really promising cancer research," she said. "While it is basic science, the possibility of the work translating into clinical application is very high. It is our hope that maspin may be ready for clinical testing within the next two years."

To find how the gene affects breast cancer cells, UI investigators used a recombinant form of maspin from LXR Biotechnology, Inc., a drug discovery and development firm based in Richmond, Calif. Richard E.B. Seftor, Ph.D., UI research scientist, and others in Hendrix's laboratory showed how maspin inhibited the breast cancer cells' ability to grow and spread. Maspin alters the profile of the cancer cells' surface binding molecules, increases the cells' selective adhesion to a common protein in the body called fibronectin, and reverts the cell from a malignant cell to a more benign, compact epithelium.

Maspin occurs naturally in the cells of normal breast tissue and helps maintain the normal tissue state; however, until recently no one knew about the gene. It was not until 1994 that researchers at the Dana Farber Cancer Institute and Harvard Medical School, along with Hendrix's lab, first reported the discovery of maspin and its ability to slow the growth and spread of breast tumors. Hendrix was working at St. Louis University Health Sciences Center at the time.

"We still do not understand what causes some women to lose maspin expression and develop breast cancer," Hendrix said. "But it is evident from our studies that maspin plays a key role in the maintenance of the normal cell phenotype."

Although the 1994 findings were significant, lack of knowledge concerning the gene's molecular and biological mechanisms of action has prevented researchers from developing maspin as a potential diagnostic and therapeutic tool for fighting breast cancer. Now that the UI team has made initial strides into understanding how maspin affects breast cancer cells, the UI researchers plan to conduct molecular experiments to look at the regulation of this important tumor suppressor gene.