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

doi:10.1016/j.ccr.2010.10.025

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

Research output: Contribution to journal › Article

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 language	English (US)
Pages (from-to)	423-435
Number of pages	13
Journal	Cancer Cell
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2010.10.025
State	Published - 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

Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-Mediated Src activation and PTEN inactivation. / Liang, Ke; Esteva, Francisco J.; Albarracin, Constance; Stemke-Hale, Katherine; Lu, Yang; Bianchini, Giampaolo; Yang, Ching Yi; Li, Yong; Li, Xinqun; Chen, Chun Te; Mills, Gordon B.; Hortobagyi, Gabriel N.; Mendelsohn, John; Hung, Mien Chie; Fan, Zhen.

In: Cancer Cell, Vol. 18, No. 5, 16.11.2010, p. 423-435.

Research output: Contribution to journal › Article

Liang, K, Esteva, FJ, Albarracin, C, Stemke-Hale, K, Lu, Y, Bianchini, G, Yang, CY, Li, Y, Li, X, Chen, CT, Mills, GB, Hortobagyi, GN, Mendelsohn, J, Hung, MC & Fan, Z 2010, 'Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-Mediated Src activation and PTEN inactivation', Cancer Cell, vol. 18, no. 5, pp. 423-435. https://doi.org/10.1016/j.ccr.2010.10.025

Liang, Ke ; Esteva, Francisco J. ; Albarracin, Constance ; Stemke-Hale, Katherine ; Lu, Yang ; Bianchini, Giampaolo ; Yang, Ching Yi ; Li, Yong ; Li, Xinqun ; Chen, Chun Te ; Mills, Gordon B. ; Hortobagyi, Gabriel N. ; Mendelsohn, John ; Hung, Mien Chie ; Fan, Zhen. / Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-Mediated Src activation and PTEN inactivation. In: Cancer Cell. 2010 ; Vol. 18, No. 5. pp. 423-435.

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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.",

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AU - Li, Yong

AU - Li, Xinqun

AU - Chen, Chun Te

AU - Mills, Gordon B.

AU - Hortobagyi, Gabriel N.

AU - Mendelsohn, John

AU - Hung, Mien Chie

AU - Fan, Zhen

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10.1016/j.ccr.2010.10.025