Suppressing NRIP1 inhibits growth of breast cancer cells in vitro and in vivo.
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.
Division of Geriatrics, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA.
Moammir H
MH
Aziz
Department of Medical Microbiology and Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA.
Xundi
X
Chen
Zhongda Hospital, Southeast University of China, Nanjing 210009, China.
Qi
Q
Zhang
Department of Pathology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA.
Chad
C
DeFrain
Division of Geriatrics, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA.
Jared
J
Osland
Department of Oncology, Nanjing Junxie Hospital, Nanjing 210002, China.
Yizhou
Y
Luo
Zhongda Hospital, Southeast University of China, Nanjing 210009, China.
Xin
X
Shi
Division of Geriatrics, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA.|Department of Medical Microbiology and Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA.
Rong
R
Yuan
D015127:9,10-Dimethyl-1,2-benzanthracene; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000078723:Nuclear Receptor Interacting Protein 1; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; C000627127:NRIP1 protein, human; C000627128:Nrip1 protein, mouse; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D015127:9,10-Dimethyl-1,2-benzanthracene
NRIP1; apoptosis; breast cancer; cell survival; human tissue array