The University Record, April 15, 2002

U-M team investigating marker that may predict breast cancer

By Kara Gavin
Health System Public Relations

A tiny protein called RhoC, found in breast tumors, may someday give doctors and patients an early warning system that could spot dangerously aggressive breast cancer long before it begins to spread, and identify the need for aggressive treatment.

A test to detect the protein is still more than a year away from clinical trials. But promising early results show that RhoC can serve as a marker for breast tumors that are most likely to spread, or metastasize. even identifying them when they’re less than a centimeter in diameter.

Physicians from the Comprehensive Cancer Center developed the test based on their prior research on the RhoC gene, and proved its effectiveness in 182 tissue samples from the U-M’s breast cancer library. Results were presented April 9 at the meeting of the American Association for Cancer Research.

“This is a very promising marker for small but invasive breast cancers that may metastasize, which right now are hard to identify,” says lead author Celina Kleer, assistant professor of pathology at the Medical School who specializes in breast cancer. “While more research is needed before clinical testing can begin, we hope it will help identify early-stage cancer that could be vulnerable to aggressive treatment, perhaps with drugs that target Rho protein.”

Kleer and her colleagues, including experienced RhoC researchers Sofia Merajver, associate professor of internal medicine, and Kenneth van Golen, assistant professor of internal medicine, embarked on the study to find out how much RhoC was produced in different kinds of breast cancer cells, compared with normal breast cells.

Previously, they had shown that the RhoC gene was overexpressed in inflammatory breast cancer, a particularly deadly variety that grows and metastasizes quickly. Overexpression of the gene, they believed, also might occur in other kinds of aggressive breast cancer—leading to larger quantities of the RhoC protein in cells of those cancers.

RhoC, whose full name is RhoC-GTPase, is an enzyme involved in changing the internal skeleton of a cell—changes that allow a cell to polarize or move. That ability is important in muscle cells, which produce a lot of RhoC. But in cancerous non-muscle cells, RhoC is key to the structural changes that give a cell the ability to break off from a tumor, float through the body in the bloodstream, and take hold in a satellite location—in other words, to metastasize.

In finding the inflammatory breast cancer correlation, the U-M team was the first to show that RhoC, already implicated in liver, pancreas and skin cancer, was also involved in breast cancer. U-M researchers, led by Merajver, showed that transplanting the RhoC gene into normal breast cells in mice transforms those cells into cancerous ones with metastatic potential.

Kleer, Merajver, van Golen and their colleagues are preparing to examine even more breast samples for the presence of RhoC, to see if their initial results hold up. The team is also in the process of planning clinical studies on the predictive power of RhoC.

The study was funded by the National Institutes of Health, the Department of Defense’s breast cancer research program, and a grant from the John and Suzanne Munn Endowment at the U-M Comprehensive Cancer Center. For more information, visit www.med.umich.edu/opm/newspage/rhocbc.htm