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

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

Access to Document

10.1016/j.ccr.2010.10.025

Fingerprint Dive into the research topics of 'Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-Mediated Src activation and PTEN inactivation'. Together they form a unique fingerprint.

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.

@article{55accf3afbd3467aab045718fa9f4686,

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

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.",

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

year = "2010",

month = nov,

day = "16",

doi = "10.1016/j.ccr.2010.10.025",

language = "English (US)",

volume = "18",

pages = "423--435",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-Mediated Src activation and PTEN inactivation

AU - Liang, Ke

AU - Esteva, Francisco J.

AU - Albarracin, Constance

AU - Stemke-Hale, Katherine

AU - Lu, Yang

AU - Bianchini, Giampaolo

AU - Yang, Ching Yi

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

PY - 2010/11/16

Y1 - 2010/11/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78249236544&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78249236544&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2010.10.025

DO - 10.1016/j.ccr.2010.10.025

M3 - Article

C2 - 21075308

AN - SCOPUS:78249236544

VL - 18

SP - 423

EP - 435

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 5

ER -