Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway

• Published in: British journal of cancer 2013-06, Vol.108 (12), p.2590-2600
• Main Authors: Pandey, P, Seshacharyulu, P, Das, S, Rachagani, S, Ponnusamy, M P, Yan, Y, Johansson, S L, Datta, K, Fong Lin, M, Batra, S K
• Format: Article
• Language: English
• Subjects: 631/208/199; 631/80/86; 692/420; 692/699/67/589/466; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Androgens; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; Cell growth; Cell Line, Tumor; Disease; Disease Progression; Down-Regulation - physiology; Drug Resistance; Enzyme Activation - genetics; Enzymes; Epidemiology; Gene Expression Regulation, Enzymologic - physiology; Gene Expression Regulation, Neoplastic - physiology; Genes; Genetics and Genomics; Humans; Kinases; Male; Medical research; Medical sciences; Metastasis; Models, Biological; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Metastasis; Nephrology. Urinary tract diseases; Oncogene Protein v-akt - metabolism; Oncology; Pathogenesis; Phosphatase; Phosphorylation; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - metabolism; Protein Phosphatase 2 - physiology; Protein Subunits - genetics; Protein Subunits - metabolism; Proteins; Signal transduction; Signal Transduction - genetics; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.160

Background: Protein phosphatase 2A (PP2A) is a dephosphorylating enzyme, loss of which can contribute to prostate cancer (PCa) pathogenesis. The aim of this study was to analyse the transcriptional and translational expression patterns of individual subunits of the PP2A holoenzyme during PCa progression. Methods: Immunohistochemistry (IHC), western blot, and real-time PCR was performed on androgen-dependent (AD) and androgen-independent (AI) PCa cells, and benign and malignant prostate tissues for all the three PP2A (scaffold, regulatory, and catalytic) subunits. Mechanistic and functional studies were performed using various biochemical and cellular techniques. Results: Through immunohistochemical analysis we observed significantly reduced levels of PP2A-A and -B′ γ subunits ( P