Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-Mediated Src activation and PTEN inactivation

Ke Liang, Francisco J. Esteva, Constance Albarracin, Katherine Stemke-Hale, Yang Lu, Giampaolo Bianchini, Ching Yi Yang, Yong Li, Xinqun Li, Chun Te Chen, Gordon B. Mills, Gabriel N. Hortobagyi, John Mendelsohn, Mien Chie Hung, Zhen Fan

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    110 Scopus citations

    Abstract

    We found that the receptor for erythropoietin (EpoR) is coexpressed with human epidermal growth factor receptor-2 (HER2) in a significant percentage of human breast tumor specimens and breast cancer cell lines. Exposure of HER2 and EpoR dual-positive breast cancer cells to recombinant human erythropoietin (rHuEPO) activated cell signaling. Concurrent treatment of the cells with rHuEPO and trastuzumab reduced the cells' response to trastuzumab both in vitro and in vivo. We identified Jak2-mediated activation of Src and inactivation of PTEN as underlying mechanisms through which rHuEPO antagonizes trastuzumab-induced therapeutic effects. Furthermore, we found that compared with administration of trastuzumab alone, concurrent administration of rHuEPO and trastuzumab correlated with shorter progression-free and overall survival in patients with HER2-positive metastatic breast cancer.

    Original languageEnglish (US)
    Pages (from-to)423-435
    Number of pages13
    JournalCancer Cell
    Volume18
    Issue number5
    DOIs
    StatePublished - Nov 16 2010

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    ASJC Scopus subject areas

    • Oncology
    • Cell Biology
    • Cancer Research

    Cite this

    Liang, K., Esteva, F. J., Albarracin, C., Stemke-Hale, K., Lu, Y., Bianchini, G., Yang, C. Y., Li, Y., Li, X., Chen, C. T., Mills, G. B., Hortobagyi, G. N., Mendelsohn, J., Hung, M. C., & Fan, Z. (2010). Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-Mediated Src activation and PTEN inactivation. Cancer Cell, 18(5), 423-435. https://doi.org/10.1016/j.ccr.2010.10.025