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Human Prostatic Acid Phosphatase in Prostate Carcinogenesis

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Prostate Cancer

Part of the book series: Protein Reviews ((PRON,volume 16))

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Abstract

Human prostatic acid phosphatase (PAcP) is classically known as a prostate epithelium-specific differentiation antigen and was used as a surrogate marker for detecting prostate cancer (PCa) and monitoring its progression until the availability of prostate-specific antigen. Mature human PAcP protein is a 100 kDa glycoprotein containing two subunits of approximately 50 kDa each. Classically, two forms of human PAcP proteins have been identified: the cellular form (cPAcP) and the secretory form (sPAcP). Recent studies reveal the existence of a transmembrane form (TM-PAcP). While the function of sPAcP and TM-PAcP in human remains under further investigation, cPAcP functions as a neutral protein tyrosine phosphatase in PCa cells and dephosphorylates human epidermal growth factor receptor-2 (HER-2/ErbB-2/Neu) resulting in decreased cell growth as well as tumor suppression. Clinically, cPAcP levels decrease in PCa tissues and correlate with PCa progression, despite elevated levels of sPAcP in circulation. Data from xenograft animal models validate the tumor suppressor activity of cPAcP in prostate carcinomas. Further, activation of ErbB-2 upon knockdown of cPAcP expression results in a castration-resistant phenotype. Expression of PAcP is regulated by different factors in human PCa cells. PAcP is also a useful immunogen in PCa immunotherapy. Further investigation of the regulatory mechanism of cPAcP expression will likely provide valuable insights into novel PCa therapy.

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Abbreviations

Ab:

Antibody

AcP:

Acid phosphatase

ADT:

Androgen deprivation therapy

APCs:

Antigen-presenting cells

CRPCa:

Castration-resistant prostate cancer

DHT:

5α-dihydrotestosterone

EGF:

Epidermal growth factor

EGFR:

EGF receptor

FBS:

Fetal bovine serum

HDAC:

Histone deacetylase

HER-2/ErbB-2/neu:

Human epidermal growth factor receptor-2

PAcP:

Prostatic acid phosphatase

PCa:

Prostate cancer

PI3K:

Phosphoinositide 3-kinase

pIs:

Isoelectric point

PKC:

Protein kinase C

PSA:

Prostate-specific antigen

PTP:

Protein tyrosine phosphatase

p-Tyr:

Phosphotyrosine

TM-PAcP:

Transmembrane PAcP

Tyr-P:

Tyrosine phosphorylation

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Acknowledgments

This book chapter preparation was supported in part by Grants CA88184 (NIH), PC050769 (DoD), PC074289 (DOD) and the Nebraska Research Initiative. We also thank previous lab members for their contributions and efforts on prostatic acid phosphatase project.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    Sakthivel Muniyan Ph.D., Yu-Wei Chou Ph.D. & Shou-Qiang Ou-Yang Ph.D.

  2. Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198, USA

    Ming-Fong Lin Ph.D.

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  1. Sakthivel Muniyan Ph.D.
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  2. Yu-Wei Chou Ph.D.
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Correspondence to Ming-Fong Lin Ph.D. .

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  1. , Depts of Urology, and, Mayo Clinic College of Medicine, 200 1st Street SW., Rochester, 55905, Minnesota, USA

    Donald J. Tindall

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Muniyan, S., Chou, YW., Ou-Yang, SQ., Lin, MF. (2013). Human Prostatic Acid Phosphatase in Prostate Carcinogenesis. In: Tindall, D. (eds) Prostate Cancer. Protein Reviews, vol 16. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6828-8_12

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