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    題名: In Vivo Targeting of ADAM9 Gene Expression Using Lentivirus-Delivered shRNA Suppresses Prostate Cancer Growth by Regulating REG4 Dependent Cell Cycle Progression
    作者: Liu, Che-Ming;Liu, Che-Ming;謝嘉玲;Hsieh, Chia-Ling;He, Yun-Chi;He, Yun-Chi;Liang, Ji-An;Liang, Ji-An;Hsie, Teng-Fu;Hsieh, Teng-Fu;Josson, Sajni;Josson, Sajni;Leland, W.K.;Leland, W.K.Chung;洪明奇;Hung, Mien-Chie;Shian-Ying, S;Shian-Ying Sung
    貢獻者: 生物科技學系
    日期: 201301
    上傳時間: 2013-10-29 10:54:46 (UTC+8)
    摘要: Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM) 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA) significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4) expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21 Cip1/WAF1, which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer.
    關聯: PLoS One
    顯示於類別:[生物科技學系] 期刊論文

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