The Ramazzini Institute
for Occupational and Environmental Health Research   

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     The lack of success in breast cancer therapies often happens because the drug can’t distinguish between good cells and bad cells. A new study shows that cancer is not the event of one gene, but an army of genes and it looks like pRb2/p130 is one of the generals.
     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 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,” was published in the June 5 issue of Oncogene.
     In the study, led by Dr. Antonio 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.
    The lead author Dr. Marcella Macaluso, a research associate at the Sbarro Institute and a member of the Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors at the University of Palermo, says the next step for researchers is to figure out how they can restore pRb2/p130’s correct communication or dialogue with the molecules in order to have the estrogen receptor alpha correctly express on the tumor cells.  By understanding this mechanism of how Rb2 recruits molecules, she says, researchers will be able to eventually design drugs that are very precise in the target they recognize.
     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 cells anymore,” says Giordano.  “It cannot distinguish between the good cells and the bad cells. The study shows that cancer is not the event of one gene, but an army of genes and it looks like pRb2/p130 is one of the generals.”