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

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Abstract

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-Bγ subunits (P<0.001 and P=0.0002) in PCa specimens compared with benign prostate. Contemporarily, there was no significant difference in PP2A-C subunit expression between benign and malignant tissues. Similar to the expression pattern observed in tissues, the endogenous levels of PP2A-A and Bγ subunits were abrogated from the low metastatic to high metastatic and AD to AI cell line models, without any change in the catalytic subunit expression. Furthermore, using in vitro studies we demonstrated that PP2A-Aa scaffold subunit has a role in dampening AKT, β-catenin, and FAK (focal adhesion kinase) signalling. Conclusion: We conclude that loss of expression of scaffold and regulatory subunits of PP2A is responsible for its altered function during PCa pathogenesis.

Original languageEnglish (US)
Pages (from-to)2590-2600
Number of pages11
JournalBritish journal of cancer
Volume108
Issue number12
DOIs
StatePublished - Jun 25 2013

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Protein Phosphatase 2
Prostatic Neoplasms
Androgens
Prostate
Catalytic Domain
Catenins
Focal Adhesion Protein-Tyrosine Kinases
Holoenzymes
Phosphoprotein Phosphatases
Real-Time Polymerase Chain Reaction
Western Blotting
Immunohistochemistry
Cell Line
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{6d14e23da83c4df3acd126f9106522e0,
title = "Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway",
abstract = "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-Bγ subunits (P<0.001 and P=0.0002) in PCa specimens compared with benign prostate. Contemporarily, there was no significant difference in PP2A-C subunit expression between benign and malignant tissues. Similar to the expression pattern observed in tissues, the endogenous levels of PP2A-A and Bγ subunits were abrogated from the low metastatic to high metastatic and AD to AI cell line models, without any change in the catalytic subunit expression. Furthermore, using in vitro studies we demonstrated that PP2A-Aa scaffold subunit has a role in dampening AKT, β-catenin, and FAK (focal adhesion kinase) signalling. Conclusion: We conclude that loss of expression of scaffold and regulatory subunits of PP2A is responsible for its altered function during PCa pathogenesis.",
author = "P. Pandey and P. Seshacharyulu and S. Das and Satyanarayana Rachagani and {Palanimuthu Ponnusamy}, Moorthy and Ying Yan and Johansson, {S. L.} and Kaustubh Datta and Ming-Fong Lin and Batra, {Surinder Kumar}",
year = "2013",
month = "6",
day = "25",
doi = "10.1038/bjc.2013.160",
language = "English (US)",
volume = "108",
pages = "2590--2600",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "12",

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TY - JOUR

T1 - Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway

AU - Pandey, P.

AU - Seshacharyulu, P.

AU - Das, S.

AU - Rachagani, Satyanarayana

AU - Palanimuthu Ponnusamy, Moorthy

AU - Yan, Ying

AU - Johansson, S. L.

AU - Datta, Kaustubh

AU - Lin, Ming-Fong

AU - Batra, Surinder Kumar

PY - 2013/6/25

Y1 - 2013/6/25

N2 - 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-Bγ subunits (P<0.001 and P=0.0002) in PCa specimens compared with benign prostate. Contemporarily, there was no significant difference in PP2A-C subunit expression between benign and malignant tissues. Similar to the expression pattern observed in tissues, the endogenous levels of PP2A-A and Bγ subunits were abrogated from the low metastatic to high metastatic and AD to AI cell line models, without any change in the catalytic subunit expression. Furthermore, using in vitro studies we demonstrated that PP2A-Aa scaffold subunit has a role in dampening AKT, β-catenin, and FAK (focal adhesion kinase) signalling. Conclusion: We conclude that loss of expression of scaffold and regulatory subunits of PP2A is responsible for its altered function during PCa pathogenesis.

AB - 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-Bγ subunits (P<0.001 and P=0.0002) in PCa specimens compared with benign prostate. Contemporarily, there was no significant difference in PP2A-C subunit expression between benign and malignant tissues. Similar to the expression pattern observed in tissues, the endogenous levels of PP2A-A and Bγ subunits were abrogated from the low metastatic to high metastatic and AD to AI cell line models, without any change in the catalytic subunit expression. Furthermore, using in vitro studies we demonstrated that PP2A-Aa scaffold subunit has a role in dampening AKT, β-catenin, and FAK (focal adhesion kinase) signalling. Conclusion: We conclude that loss of expression of scaffold and regulatory subunits of PP2A is responsible for its altered function during PCa pathogenesis.

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DO - 10.1038/bjc.2013.160

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JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

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