Author/Authors :
Liang، نويسنده , , Ke and Esteva، نويسنده , , Francisco J. and Albarracin، نويسنده , , Constance and Stemke-Hale، نويسنده , , Katherine and Lu، نويسنده , , Yang and Bianchini، نويسنده , , Giampaolo and Yang، نويسنده , , Ching-Yi and Li، نويسنده , , Yong and Li، نويسنده , , Xinqun and Chen، نويسنده , , Chun-Te and Mills، نويسنده , , Gordon B. and Hortobagyi، نويسنده , , Gabriel N. and Mendelsohn، نويسنده , , John and Hung، نويسنده , , Mien-Chie and Fan، نويسنده , , Zhen، نويسنده ,
Abstract :
Summary
nd 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 cellsʹ 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.
