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

Oncogene volume 19, pages 2664–2677 (2000)Cite this article

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, but not the protein level, of ErbB-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.

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Acknowledgements

We thank Dr Hsing-Jien Kung for his gift of pCMV-HER2 plasmid, Dr Chawnshang Chang for anti-AR antiserum, Dr Robert Lewis for monoclonal anti-Myc tag antibody and Ms Fen-Fen Lin for the technical assistance of initial tissue culture works. This study was supported in part by a NIH grant CA72274, Nebraska Cancer and Smoking Diseases Research Program LB 506 grant #2000-19, UNMC Eppley Cancer Center grant LB 595 and BMB Prostate Cancer Research Program to M-F Lin and Graduate Study Fellowships from the Graduate Studies Office, University of Nebraska Medical Center to T-C Meng and M-S Lee.

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

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

  2. Section of Urologic Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, 68198, Nebraska, NE, USA

    Ming-Fong Lin

  3. Eppely Cancer Institute, University of Nebraska Medical Center, Omaha, 68198, Nebraska NE, USA

    Ming-Fong Lin

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Meng, TC., Lee, MS. & Lin, MF. Interaction between protein tyrosine phosphatase and protein tyrosine kinase is involved in androgen-promoted growth of human prostate cancer cells. Oncogene 19, 2664–2677 (2000). https://doi.org/10.1038/sj.onc.1203576

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