Suppressing NRIP1 inhibits growth of breast cancer cells in vitro and in vivo
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Moammir H. Aziz1, Xundi Chen2, Qi Zhang3, Chad DeFrain4, Jared Osland1, Yizhou Luo5, Xin Shi3, Rong Yuan1,2
1Division of Geriatrics, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA
2Department of Medical Microbiology and Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA
3Zhongda Hospital, Southeast University of China, Nanjing, China 210009
4Department of Pathology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA
5Department of Oncology, Nanjing Junxie Hospital, Nanjing, China, 210002
Rong Yuan, e-mail: [email protected]
Keywords: NRIP1, breast cancer, human tissue array, apoptosis, cell survival
Received: April 13, 2015 Accepted: October 03, 2015 Published: October 15, 2015
Earlier age at menarche is a major risk factor for breast cancer. Our previous study identified Nrip1 (also known as Rip140) as a candidate gene for delaying female sexual maturation (FSM) and found that knocking out Nrip1 could significantly delay FSM in mice. To investigate the effects of NRIP1 in breast cancer we used human cell lines and tissue arrays along with an in vivo study of DMBA-induced carcinogenesis in Nrip1 knockout mice. Analysis of tissue arrays found that NRIP1 is elevated in tumors compared to cancer adjacent normal tissue. Interestingly, in benign tumors NRIP1 levels are higher in the cytosol of stromal cells, but NRIP1 levels are higher in the nuclei of epithelial cells in malignancies. We also found overexpression of NRIP1 in breast cancer cell lines, and that suppression of NRIP1 by siRNA in these cells significantly induced apoptosis and inhibited cell growth. Furthermore, in vivo data suggests that NRIP1 is upregulated in DMBA-induced breast cancer. Importantly, we found that DMBA-induced carcinogenesis is suppressed in Nrip1 knockdown mice. These findings suggest that NRIP1 plays a critical role in promoting the progression and development of breast cancer and that it may be a potential therapeutic target for the new breast cancer treatments.
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