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

Abdulrahman Alwhaibi, Ravindra Kolhe, Fei Gao, Ewan K Cobran, Payaningal R Somanath

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)317-336
Number of pages20
JournalOncoscience
Volume6
Issue number5-6
DOIs
StatePublished - May 2019

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