The prognosis for breast cancer patients often depends on whether their tumor cells make estrogen receptor and can, therefore, respond to the hormone. Breast cancer tumors that make estrogen receptor tend to have a better prognosis than tumors without the receptor. About a quarter of breast cancers do not respond to estrogen.

"If we can figure out at a molecular level why some breast cancers make the receptor and respond to hormone, we may be able to develop novel treatments for those tumors that don't normally respond to hormonal therapy," explained Ronald Weigel, M.D., Ph.D., head of UI Hospitals and Clinics surgery department and UI professor and head of surgery, and principal investigator of the study.

Tumors that express estrogen receptor can be effectively treated with hormonal therapies like tamoxifen and aromatase inhibitors. Breast cancer cells that express receptor also act less abnormally than tumor cells that do not make this protein.

The UI researchers will focus on understanding how production, or expression, of estrogen receptor is controlled. Weigel and colleagues will build on earlier studies that identified a protein called AP2 as a key regulator of estrogen receptor expression.

The UI team will investigate the molecular mechanisms that control the ability of AP2 to turn on estrogen receptor expression. The researchers also will follow up on a discovery from Weigel's lab that AP2 interacts with the tumor suppressor protein p53. This interaction appears to inhibit AP2's ability to turn on estrogen receptor expression and may represent another pathway that could be manipulated to reactivate receptor expression.

"Understanding AP2 pathways may allow scientists to find ways to re-express estrogen receptor to either augment hormone response in weakly responsive breast cancers or potentially to make an unresponsive cancer a responsive one," said Weigel, who also is a member of the Holden Comprehensive Cancer Center at the UI.

For more information:

National Cancer Institute

Holden Comprehensive Cancer Center