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 | |
| State | Published - Nov 16 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research
Cite this
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; 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
}
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
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.
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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
VL - 18
SP - 423
EP - 435
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 5
ER -