Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells

Authors

  • Laurie Feldman,

    Corresponding author
    1. Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
    2. Department of Medicine, Harvard Medical School, Boston, Massachusetts
    • Laboratory for Cell and Molecular Biology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue-W/BL 548, Boston, MA 02215.
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  • Yuxun Wang,

    1. Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
    2. Department of Medicine, Harvard Medical School, Boston, Massachusetts
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  • Johng S. Rhim,

    1. Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, Maryland
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  • Nandita Bhattacharya,

    1. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
    2. Department of Medicine, Harvard Medical School, Boston, Massachusetts
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  • Massimo Loda,

    1. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
    2. Department of Medicine, Harvard Medical School, Boston, Massachusetts
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  • Arthur J. Sytkowski

    1. Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
    2. Department of Medicine, Harvard Medical School, Boston, Massachusetts
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Abstract

BACKGROUND

Erythropoietin (Epo), the principal regulator of erythroid progenitor survival, growth, and differentiation, initiates its action by binding to its cognate cell surface receptor (EpoR). EpoR have been identified on a variety of non-hematopoietic cells, both normal and malignant, however, little is known about the function of EpoR on malignant cells.

METHODS

RT-PCR, Western blotting, and immunohistochemistry were used to demonstrate that prostate cancer cells express EpoR at both the gene and protein level. Cell proliferation assays and STAT5 phosphorylation were used to demonstrate Epo's mitogenic action and intracellular signaling, respectively.

RESULTS

We have demonstrated that transformed prostate epithelial and prostate cancer cell lines, as well as primary prostate tissue, express the EpoR. Importantly, the EpoR on prostate cells are functional, as demonstrated by the observation that each of the cell lines exhibited a dose-dependent proliferative response to Epo, and that Epo triggered STAT5b phosphorylation in the cells.

CONCLUSION

Human prostatic epithelial cells and prostate cancer cells express functional EpoR, and Epo serves as a growth factor for these cells. These results have implications for our understanding of normal prostatic growth and development and of the pathobiology of human prostate cancer. © 2005 Wiley-Liss, Inc.

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