Researchers from the Case Western Reserve University School of Medicine have discovered a new breast cancer gene that may play a role in estrogen-induced breast cancers

The lead researchers in this study, Monica M. Montano and doctoral student Bryan M. Wittmann in the Case department of pharmacology, were searching for proteins that interact with the estrogen receptor when they discovered Estrogen Down-regulated Gene 1 (EDG1). EDG1 was found to suppress the normal function of estrogen receptors and inhibit breast cell growth, thereby, possibly acting as a tumor suppressor.

The team's findings were published in a recent issue of "Cancer Research." The article, "Identification of a Novel Inhibitor of Breast Cell Growth That Is Down-Regulated by Estrogens and Decreased in Breast Tumors," was coauthored by Nancy Wang, a University Hospitals of Cleveland pathologist.

The study indicates that EDG1 levels are reduced by estrogens and show decreased expression in breast tumors. The link to estrogen is important because lifetime exposure to estrogen is a major risk factor
for breast cancer. The growth of more than 95 percent of all breast cancers is initially dependent upon the presence and activation of an estrogen receptor. Montano and her team are suggesting that reduced levels of genes like EDG1 play a role in estrogen-induced breast cancer development.

Wittmann analyzed the presence of EDG1 in breast tumor cells and compared it to the presence of the gene in normal breast cells in 43 patients. He found that EDG1 levels are significantly higher in normal breast cells as compared to breast tumor cells. He also found that tumor cells that express EDG1 are more likely to express the estrogen receptor. Tumors that are estrogen-receptor positive have a better prognosis, while breast cancer tumors that undergo high growth rates-and are less likely to express EDG1-have a worse prognosis.

"It's possible that by decreasing the levels of tumor suppressors like EDG1, estrogen is inducing breast tumor growth," Montano said. "Another possibility is that estrogen has DNA-damaging effects, thereby allowing for increased mutation rates."

More important, Montano said, is that EDG1 expression was found to be significantly lower in normal breast cells adjacent to Grade III tumors, which carry a worse prognosis, versus normal breast cells adjacent to Grade I and II tumors. She added that EDG1 could be used in the future as a tool in diagnosing breast cancer.

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