Progesterone activates USF-1 in estrogen induced mammary carcinogenesis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 292-325-Breast & Prostate Cancer
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-304
Thiyagarajan Boopalan*1, Arunkumar Arumugam2, Sushmita B Nandy2, Rebecca Lopez3, Christina Gutierrez4 and Rajkumar Lakshmanaswamy5
1Texas Tech Univ, El Paso, TX, 2Texas Tech University Health Sci, El Paso, TX, 3Texas Tech University Health Sciences, El Paso, TX, 4Texas Tech University Health Sciences Center, El Paso, TX, 5Texas Tech Univ Health Sci Ctr, El Paso, TX
Breast cancer continues to be the leading cause of death in women; prolonged exposure to ovarian hormones estrogen and progesterone increases the risk of breast cancer. Evidence suggests that estrogen is primarily involved in the development of mammary carcinogenesis; very few studies have illustrated the role of progesterone in breast cancer. In our earlier study, we demonstrated the precise role of progesterone in breast cancer, yet the underlying mechanism is poorly understood. Here we show that progesterone mediates estrogen induced mammary carcinogenesis by activating upstream stimulatory factor 1 (USF-1) through activation of RANKL/RANK and NF-κB in an AKT dependent manner in ACI rat model and in MCF 7 cells. We show that RANKL/RANK activation induced the phosphorylation of AKT and increased NF-κB expression. Activation of AKT resulted in inhibition of apoptosis by increasing the expression of anti apoptotic protein Bcl2. In the present study, we also show that inhibition of progesterone with anti progesterone mifepristone significantly reduced the tumor incidence in ACI rats and cell proliferation in    MCF 7 cells. Further, mifepristone also inhibited the activation of RANKL/RANK, USF-1 and NF-κB, illustrating that estrogen induced mammary carcinogenesis is dependent on progesterone. Our finding suggests that progesterone may be an important target in inhibiting estrogen induced mammary carcinogenesis through regulation of RANKL/RANK, USF 1 and NF-κB.

Nothing to Disclose: TB, AA, SBN, RL, CG, RL

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