Interaction between protein tyrosine phosphatase and protein tyrosine kinase is involved in androgen-promoted growth of human prostate cancer cells

Tzu Ching Meng, Ming Shyue Lee, Ming-Fong Lin

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Steroid hormones play key roles in regulating cell proliferation and differentiation in targeting tissues. However, in advanced cancers, the steroid hormone regulation is frequently attenuated through a yet unknown mechanism even in the presence of functional steroid hormone receptors. We investigate the functional role of tyrosine phosphorylation signaling in the hormone-refractory growth of human prostate tumors. Initial studies demonstrate that the androgen-responsive phenotype of human prostate cancer cells associates with a low phosphotyrosine (p-Tyr) level of ErbB-2, which is regulated by cellular prostatic acid phosphatase (PAcP), a protein tyrosine phosphatase. In prostate cancer cells, the p-Tyr level, hut not the protein level, of ErbR-2 inversely correlates with the androgen-responsiveness of cell proliferation. Androgen-stimulated cell growth concurs with a down-regulation of cellular PAcP, an elevated p-Tyr level of ErbB-2, and the activation of mitogen-activated protein kinases. Furthermore, only the ErbB-2 inhibitor AG 879, but not the EGFR inhibitor AG 1478, abolishes androgen-induced cell proliferation. Forced expression of ErbB-2 can also attenuate androgen promotion of cell growth. Data taken collectively conclude that in human prostate cancer cells, the tyrosine phosphorylation of ErbB-2 regulated by cellular PAcP plays a key role in regulating androgen-mediated proliferation signaling.

Original languageEnglish (US)
Pages (from-to)2664-2677
Number of pages14
JournalOncogene
Volume19
Issue number22
DOIs
StatePublished - May 18 2000

Fingerprint

Protein Tyrosine Phosphatases
Protein-Tyrosine Kinases
Androgens
Prostatic Neoplasms
Phosphotyrosine
Growth
Cell Proliferation
Hormones
Tyrosine
Steroids
Phosphorylation
Human Growth Hormone
Steroid Receptors
Mitogen-Activated Protein Kinase 1
Prostate
Cell Differentiation
Neoplasms
Down-Regulation
Phenotype
prostatic acid phosphatase

Keywords

  • Androgen responsiveness
  • ErbB-2
  • Human prostate cancer
  • Prostatic acid phosphatase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Interaction between protein tyrosine phosphatase and protein tyrosine kinase is involved in androgen-promoted growth of human prostate cancer cells. / Meng, Tzu Ching; Lee, Ming Shyue; Lin, Ming-Fong.

In: Oncogene, Vol. 19, No. 22, 18.05.2000, p. 2664-2677.

Research output: Contribution to journalArticle

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