Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth

Tsai Der Chuang, Siu Ju Chen, Fen Fen Lin, Suresh Veeramani, Satyendra Kumar, Surinder Kumar Batra, Yaping Tu, Ming-Fong Lin

Research output: Contribution to journalArticle

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Abstract

Cellular prostatic acid phosphatase (cPAcP), an authentic tyrosine phosphatase, is proposed to function as a negative growth regulator of prostate cancer (PCa) cells in part through its dephosphorylation of ErbB-2. Nevertheless, the direct interaction between cPAcP and ErbB-2 has not been shown nor the specific dephosphorylation site of ErbB-2 by cPAcP. In this report, our data show that the phosphorylation level of ErbB-2 primarily at Tyr 1221/2 correlates with the growth rate of both LNCaP and MDA PCa2b human PCa cells. Further, cPAcP reciprocally co-immunoprecipitated with ErbB-2 in a non-permissive growth condition. Expression of wild type cPAcP, but not inactive mutant, by cDNA in cPAcP-null LNCaP C-81 cells results in decreased tyrosine phosphorylation of ErbB-2 including Tyr1221/2. Concurrently, Tyr317 phosphorylation of p52Shc, proliferating cell nuclear antigen expression, and cell growth are decreased in these cells. Conversely, decreased cPAcP expression by short hairpin RNA in LNCaP C-33 cells was associated with elevated phosphorylation of ErbB-2 initially at Tyr 1221/2. Its downstream p52Shc, ERK1/2, Akt, Src, STAT-3, and STAT-5 were activated, and cell proliferation, proliferating cell nuclear antigen, and cyclin D1 expression were increased. Stable subclones of C-33 cells by small interfering PAcP had elevated Tyr1221/2 phosphorylation of ErbB-2 and exhibited androgen-independent growth and increased tumorigenicity in xenograft female animals. In summary, our data together indicate that in prostate epithelia, cPAcP interacts with and dephosphorylates ErbB-2 primarily at Tyr1221/2 and hence blocks downstream signaling, leading to reduced cell growth. In PCa cells, decreased cPAcP expression is associated with androgen-independent cell proliferation and tumorigenicity as seen in advanced hormone-refractory prostate carcinomas.

Original languageEnglish (US)
Pages (from-to)23598-23606
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number31
DOIs
StatePublished - Jul 30 2010

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Cell growth
Phosphoric Monoester Hydrolases
Tyrosine
Prostatic Neoplasms
Phosphorylation
Growth
Proliferating Cell Nuclear Antigen
Cell proliferation
Androgens
Prostate
Cell Proliferation
prostatic acid phosphatase
Cyclin D1
Heterografts
Refractory materials
Small Interfering RNA
Animals
Epithelium
Complementary DNA
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. / Chuang, Tsai Der; Chen, Siu Ju; Lin, Fen Fen; Veeramani, Suresh; Kumar, Satyendra; Batra, Surinder Kumar; Tu, Yaping; Lin, Ming-Fong.

In: Journal of Biological Chemistry, Vol. 285, No. 31, 30.07.2010, p. 23598-23606.

Research output: Contribution to journalArticle

Chuang, Tsai Der ; Chen, Siu Ju ; Lin, Fen Fen ; Veeramani, Suresh ; Kumar, Satyendra ; Batra, Surinder Kumar ; Tu, Yaping ; Lin, Ming-Fong. / Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 31. pp. 23598-23606.
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abstract = "Cellular prostatic acid phosphatase (cPAcP), an authentic tyrosine phosphatase, is proposed to function as a negative growth regulator of prostate cancer (PCa) cells in part through its dephosphorylation of ErbB-2. Nevertheless, the direct interaction between cPAcP and ErbB-2 has not been shown nor the specific dephosphorylation site of ErbB-2 by cPAcP. In this report, our data show that the phosphorylation level of ErbB-2 primarily at Tyr 1221/2 correlates with the growth rate of both LNCaP and MDA PCa2b human PCa cells. Further, cPAcP reciprocally co-immunoprecipitated with ErbB-2 in a non-permissive growth condition. Expression of wild type cPAcP, but not inactive mutant, by cDNA in cPAcP-null LNCaP C-81 cells results in decreased tyrosine phosphorylation of ErbB-2 including Tyr1221/2. Concurrently, Tyr317 phosphorylation of p52Shc, proliferating cell nuclear antigen expression, and cell growth are decreased in these cells. Conversely, decreased cPAcP expression by short hairpin RNA in LNCaP C-33 cells was associated with elevated phosphorylation of ErbB-2 initially at Tyr 1221/2. Its downstream p52Shc, ERK1/2, Akt, Src, STAT-3, and STAT-5 were activated, and cell proliferation, proliferating cell nuclear antigen, and cyclin D1 expression were increased. Stable subclones of C-33 cells by small interfering PAcP had elevated Tyr1221/2 phosphorylation of ErbB-2 and exhibited androgen-independent growth and increased tumorigenicity in xenograft female animals. In summary, our data together indicate that in prostate epithelia, cPAcP interacts with and dephosphorylates ErbB-2 primarily at Tyr1221/2 and hence blocks downstream signaling, leading to reduced cell growth. In PCa cells, decreased cPAcP expression is associated with androgen-independent cell proliferation and tumorigenicity as seen in advanced hormone-refractory prostate carcinomas.",
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AU - Chuang, Tsai Der

AU - Chen, Siu Ju

AU - Lin, Fen Fen

AU - Veeramani, Suresh

AU - Kumar, Satyendra

AU - Batra, Surinder Kumar

AU - Tu, Yaping

AU - Lin, Ming-Fong

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