RB ASSOCIATED PROTEIN 46 AND BREAST CANCER PROGRESSION

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DESCRIPTION: (Adapted from the Investigator's Abstract): Based on their preliminary data that levels of RbAp46 expression decline during the progression of proliferative breast disease in the MCF10AT xenograft model and in malignant breast cancer cells, the investigators propose to: 1. Study the effects of constitutive expression on estrogen-stimulated progression using the MCF10AT xenograft model, and examine the levels of RbAp46 expression in human clinical samples using immunohistochemistry and/or RT-PCR. 2. Study the biological significance of the interaction between RbAp46 and the product of BRCA1 using in vivo and in vitro binding assays, as co-immunoprecipitation and GST capture assays, and RbAp46 and BRCA1 interaction and co-localization during the cell cycle and after exposure to DNA damage agents. 3. Study the molecular mechanisms by which RbAp46 inhibits cell growth and suppresses malignant transformation by examining the Ras pathway in MCF10At cells, and structure/ functional analyses to determine the domains of RbAp46 that are required for its growth inhibition and interaction with BRCA1.