title: AKT3 promotes prostate cancer proliferation cells through regulation of Akt, B-Raf, and TSC1/TSC2.
abstract: 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, GSK3β, phospho-GSK3β 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.
authors: National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.
authors: Hui-Ping
authors: HP
authors: Lin
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan.
authors: Ching-Yu
authors: CY
authors: Lin
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan.|Department of Life Sciences, National Central University, Taiwan.
authors: Chieh
authors: C
authors: Huo
authors: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan.|Medical College of Chung Shan Medical University, Taichung City, Taiwan.
authors: Yee-Jee
authors: YJ
authors: Jan
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan.|Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Jen-Chih
authors: JC
authors: Tseng
authors: National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.
authors: Shih Sheng
authors: SS
authors: Jiang
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan.
authors: Ying-Yu
authors: YY
authors: Kuo
authors: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors: Shyh-Chang
authors: SC
authors: Chen
authors: National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.
authors: Chih-Ting
authors: CT
authors: Wang
authors: Department of Medical Education and Research, China Medical University Beigan Hospital, Yunlin, Taiwan.
authors: Tzu-Min
authors: TM
authors: Chan
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan.
authors: Jun-Yang
authors: JY
authors: Liou
authors: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors: John
authors: J
authors: Wang
authors: National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.
authors: Wun-Shaing Wayne
authors: WS
authors: Chang
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan.
authors: Chung-Ho
authors: CH
authors: Chang
authors: National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.|Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan.
authors: Hsing-Jien
authors: HJ
authors: Kung
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan.|Graduate Institute of Basic Medical Science, China Medical University, Taichung City, Taiwan.|Graduate Program for Aging, China Medical University, Taichung City, Taiwan.|Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung City, Taiwan.|Ph.D. program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors: Chih-Pin
authors: CP
authors: Chuu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016208:Databases, Factual; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; C000624651:Tsc1 protein, mouse; C000624654:Tsc2 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C494918:AKT1 protein, human; C491754:AKT3 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt3; B-Raf; TSC1/2; proliferation; prostate cancer