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Cancer Cell. 2010 Nov 16;18(5):423-35. 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.

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  • 1Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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PMID:
21075308
[PubMed - indexed for MEDLINE]
PMCID:
PMC3022383
Free PMC Article

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