Oncoscience

Genome atlas analysis based profiling of Akt pathway genes in the early and advanced human prostate cancer

Abdulrahman Alwhaibi1, Ravindra Kolhe2, Fei Gao1, Ewan K. Cobran3, Payaningal R. Somanath1,4

1Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912

2Department of Pathology, Augusta University, Augusta, GA 30912

3Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Athens, GA 30602

4Department of Medicine, Vascular Biology Center and Cancer Center, Augusta University, Augusta, GA 30912

Correspondence to:

Payaningal R. Somanath, email:sshenoy@augusta.edu

Keywords: Akt1; Akt2; Akt3; cBioportal; TCGA; prostate cancer

Received: November 29, 2018 Accepted: April 22, 2019 Published: July 2, 2019

Abstract

Recent studies conducted in the mouse and cellular models suggest a stage-specific, differential effect of Akt activity modulation on tumor growth and metastasis in various cancers. In prostate cancer (PCa), although the deletion of Akt1 gene in a neuroendocrine model of TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) blunted oncogenic transformation and tumor growth, Akt1 suppression in the advanced PCa resulted in the activation of transforming growth factor-β pathway and enhanced metastasis to the lungs. Such a dual role for the Akt isoforms and its signaling partners has not been investigated in human PCa. In the current study, we performed genomic database analysis of Akt isoforms and associated pathway molecules in human prostate adenocarcinoma, castration-resistant PCa, neuroendocrine PCa and metastatic PCa for mutations, genetic alterations, mRNA and protein expressions and activating phosphorylations from cBioportal. Results from the protein data analysis from the cBioportal were compared to the results of our data on human PCa tissue analysis and the cellular effects of Akt1 suppression using MK-2206 on PCa cell aggressiveness. Our study indicates the existence of a dual role for Akt1 in PCa and warrants a large-scale analysis of the early and advanced stage PCa clinical samples for further clarity.


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