國家衛生研究院 NHRI:Item 3990099045/9236
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    題名: Akt3 promotes prostate cancer proliferation cells through regulation of Akt, B-Raf & TSC1/TSC2
    作者: Lin, HP;Lin, CY;Huo, C;Jan, YJ;Tseng, JC;Jiang, SS;Kuo, YY;Chen, SC;Wang, CT;Chan, TM;Liou, JY;Wang, J;Chang, WW;Chang, CH;Kung, HJ;Chuu, CP
    貢獻者: Institute of Molecular and Genomic Medicine;National Institute of Cancer Research;Institute of Cellular and Systems Medicine
    摘要: The qRT-PCR analysis of 139 clinical samples and analysis of 150 on-line database clinical samples indicated that AKT3 mRNA expression level was elevated in primary prostate tumors. Immunohistochemical staining of 65 clinical samples revealed that AKT3 protein expression was higher in prostate tumors of stage I, II, III as compared to nearby normal tissues. Plasmid overexpression of AKT3 promoted cell proliferation of LNCaP, PC-3, DU-145, and CA-HPV-10 human prostate cancer (PCa) cells, while knockdown of AKT3 by siRNA reduced cell proliferation. Overexpression of AKT3 increased the protein expression of total AKT, phospho-AKT S473, phospho-AKT T308, B-Raf, c-Myc, Skp2, cyclin E, GSK3beta, phospho-GSK3beta S9, phospho-mTOR S2448, and phospho-p70S6K T421/S424, but decreased TSC1 (tuberous sclerosis 1) and TSC2 (tuberous Sclerosis Complex 2) proteins in PC-3 PCa cells. Overexpression of AKT3 also increased protein abundance of phospho-AKT S473, phospho-AKT T308, and B-Raf but decreased expression of TSC1 and TSC2 proteins in LNCaP, DU-145, and CA-HPV-10 PCa cells. Oncomine datasets analysis suggested that AKT3 mRNA level was positively correlated to BRAF. Knockdown of AKT3 in DU-145 cells with siRNA increased the sensitivity of DU-145 cells to B-Raf inhibitor treatment. Knockdown of TSC1 or TSC2 promoted the proliferation of PCa cells. Our observations implied that AKT3 may be a potential therapeutic target for PCa treatment.
    日期: 2015-07-10
    關聯: Oncotarget. 2015 Jul 10;6(29):27097-27112.
    Link to: http://dx.doi.org/10.18632/oncotarget.4553
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000363161300051
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84944472711
    顯示於類別:[龔行健] 期刊論文
    [張文祥] 期刊論文
    [江士昇] 期刊論文
    [褚志斌] 期刊論文
    [張中和] 期刊論文
    [劉俊揚] 期刊論文

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