Cellular prostatic acid phosphatase: A protein tyrosine phosphatase involved in androgen-independent proliferation of prostate cancer

Suresh Veeramani, Ta Chun Yuan, Siu Ju Chen, Fen Fen Lin, Juliette E. Petersen, Syed Shaheduzzaman, Shiv Srivastava, Richard G MacDonald, Ming-Fong Lin

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Abstract

Human prostatic acid phosphatase (PAcP) was used as a valuable surrogate marker for monitoring prostate cancer prior to the availability of prostate-specific antigen (PSA). Even though the level of PAcP is increased in the circulation of prostate cancer patients, its intracellular level and activity are greatly diminished in prostate cancer cells. Recent advances in understanding the function of the cellular form of PAcP (cPAcP) have shed some light on its role in prostate carcinogenesis, which may have potential applications for prostate cancer therapy. It is now evident that cPAcP functions as a neutral protein tyrosine phosphatase (PTP) in prostate cancer cells and dephosphorylates HER-2/ErbB-2/Neu (HER-2: human epidermal growth factor receptor-2) at the phosphotyrosine (p-Tyr) residues. Dephosphorylation of HER-2 at its p-Tyr residues results in the down-regulation of its specific activity, which leads to decreases in growth and tumorigenicity of those cancer cells. Conversely, decreased cPAcP expression correlates with hyperphosphorylation of HER-2 at tyrosine residues and activation of downstream extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling, which results in prostate cancer progression as well as androgen-independent growth of prostate cancer cells. These in vitro results on the effect of cPAcP on androgen-independent growth of prostate cancer cells corroborate the clinical findings that cPAcP level is greatly decreased in advanced prostate cancer and provide insights into one of the molecular mechanisms involved in prostate cancer progression. Results from experiments using xenograft animal models further indicate a novel role of cPAcP as a tumor suppressor. Future studies are warranted to clarify the use of cPAcP as a therapeutic agent in human prostate cancer patients.

Original languageEnglish (US)
Pages (from-to)805-822
Number of pages18
JournalEndocrine-Related Cancer
Volume12
Issue number4
DOIs
Publication statusPublished - Dec 1 2005

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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