Rb2 gene may play role in determining effectiveness of drug therapies against breat cancer

The tumor suppressing gene pRb2/p130 may play a significant role in determining the effectiveness of drug therapies against breast cancer in women, according to a study by researchers at Temple University's Sbarro Institute for Cancer Research and Molecular Medicine.

The study, "pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 Multimolecular Complexes Mediate the Transcription of Estrogen Receptor-a in Breast Cancer," will be presented at an international scientific lecture on Thursday, June 5, by Antonio Giordano, M.D., Ph.D., director of the Sbarro Institute. It will also be published in the June 5 issue of Oncogene (http://www.nature.com/onc/).

In the study, led by Giordano, researchers at the Sbarro Institute looked at the estrogen receptor gene alpha, which plays a crucial role in normal breast development in women and has been linked to the development and progression of mammary carcinoma, or breast cancer.

The study found that in estrogen receptor-positive and estrogen receptor-negative mammary cell lines of women who have been affected with breast cancer, pRb2/p130 binds with the estrogen receptor gene alpha and sends out signals to engage or recruit a number of molecules.

"These key molecules together are recruited by pRb2/p130 onto the receptor gene alpha, which when expressed on mammary cell lines makes the breast tumors more responsive to treatment," says Giordano, who discovered the Rb2 gene while working at Temple's Fels Cancer Institute in the early 1990s.

The researchers discovered that in estrogen receptor-negative cell lines, pRb2/p130's signal is damaged or mutated and it recruits a different sequence of molecules which cause Rb2 to silence the expression of the estrogen receptor and block drug therapies from being successful against the cancer cells.

"There is a lack of success in therapies because the drug does not recognize the tumor

Contact: Preston M. Moretz
Temple University

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