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