AKT3 promotes prostate cancer proliferation cells through regulation of Akt, B-Raf & TSC1/TSC2
Metrics: PDF 1159 views | HTML 1899 views | ?
Hui-Ping Lin1,*, Ching-Yu Lin2,*, Chieh Huo2,3,*, Yee-Jee Jan4,5,*, Jen-Chih Tseng2,6, Shih Sheng Jiang1, Ying-Yu Kuo2, Shyh-Chang Chen4, Chih-Ting Wang1, Tzu-Min Chan7, Jun-Yang Liou2, John Wang4, Wun-Shaing Wayne Chang1, Chung-Ho Chang2, Hsing-Jien Kung1,8, Chih-Pin Chuu2,9,10,11,12
1National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan
2Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan
3Department of Life Sciences, National Central University, Taiwan
4Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan
5Medical College of Chung Shan Medical University, Taichung City, Taiwan
6Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
7Department of Medical Education and Research, China Medical University Beigan Hospital, Yunlin, Taiwan
8Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan
9Graduate Institute of Basic Medical Science, China Medical University, Taichung City, Taiwan
10Graduate Program for Aging, China Medical University, Taichung City, Taiwan
11Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung City, Taiwan
12Ph.D. program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
*These authors have contributed equally to this work
Chih-Pin Chuu, e-mail: firstname.lastname@example.org
Keywords: Akt3, prostate cancer, B-Raf, TSC1/2, proliferation
Received: April 16, 2015 Accepted: June 29, 2015 Published: July 10, 2015
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.