AKT3 promotes prostate cancer proliferation cells through regulation of Akt, B-Raf & TSC1/TSC2

Hui Ping Lin, Ching Yu Lin, Chieh Huo, Yee Jee Jan, Jen Chih Tseng, Shih Sheng Jiang, Ying Yu Kuo, Shyh Chang Chen, Chih Ting Wang, Tzu Min Chan, Jun Yang Liou, John Wang, Wun Shaing Wayne Chang, Chung Ho Chang, Hsing-Jien Kung, Chih Pin Chuu

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The qRT-PCR analysis of 139 clinical samples and analysis of 150 on-line databaseclinical samples indicated that AKT3 mRNA expression level was elevated in primaryprostate tumors. Immunohistochemical staining of 65 clinical samples revealed thatAKT3 protein expression was higher in prostate tumors of stage I, II, III as comparedto nearby normal tissues. Plasmid overexpression of AKT3 promoted cell proliferationof LNCaP, PC-3, DU-145, and CA-HPV-10 human prostate cancer (PCa) cells, whileknockdown of AKT3 by siRNA reduced cell proliferation. Overexpression of AKT3increased 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, andphospho-p70S6K T421/S424, but decreased TSC1 (tuberous sclerosis 1) and TSC2(tuberous Sclerosis Complex 2) proteins in PC-3 PCa cells. Overexpression of AKT3also increased protein abundance of phospho-AKT S473, phospho-AKT T308, andB-Raf but decreased expression of TSC1 and TSC2 proteins in LNCaP, DU-145, andCA-HPV-10 PCa cells. Oncomine datasets analysis suggested that AKT3 mRNA levelwas positively correlated to BRAF. Knockdown of AKT3 in DU-145 cells with siRNAincreased the sensitivity of DU-145 cells to B-Raf inhibitor treatment. Knockdown ofTSC1 or TSC2 promoted the proliferation of PCa cells. Our observations implied thatAKT3 may be a potential therapeutic target for PCa treatment.

Original languageEnglish (US)
Pages (from-to)27097-27112
Number of pages16
JournalOncotarget
Volume6
Issue number29
DOIs
StatePublished - 2015
Externally publishedYes

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Keywords

  • Akt3
  • B-Raf
  • Proliferation
  • Prostate cancer
  • TSC1/2

ASJC Scopus subject areas

  • Oncology

Cite this

Lin, H. P., Lin, C. Y., Huo, C., Jan, Y. J., Tseng, J. C., Jiang, S. S., Kuo, Y. Y., Chen, S. C., Wang, C. T., Chan, T. M., Liou, J. Y., Wang, J., Wayne Chang, W. S., Chang, C. H., Kung, H-J., & Chuu, C. P. (2015). AKT3 promotes prostate cancer proliferation cells through regulation of Akt, B-Raf & TSC1/TSC2. Oncotarget, 6(29), 27097-27112. https://doi.org/10.18632/oncotarget.4553