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学科主题: 临床医学
题名:
Erythropoietin receptor expression and its relationship with trastuzumab response and resistance in HER2-positive breast cancer cells
作者: Zhang, Chi; Duan, Xuening; Xu, Ling; Ye, Jingming; Zhao, Jianxin; Liu, Yinhua
关键词: Breast cancer ; Erythropoietin receptor ; HER2 ; Resistance ; Trastuzumab
刊名: BREAST CANCER RESEARCH AND TREATMENT
发表日期: 2012-12-01
DOI: 10.1007/s10549-012-2316-x
卷: 136, 期:3, 页:739-748
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: RECOMBINANT-HUMAN-ERYTHROPOIETIN ; CHEMOTHERAPY-INDUCED ANEMIA ; ADJUVANT CHEMOTHERAPY ; DOUBLE-BLIND ; ACTIVATION ; INVASIVENESS ; CONTRIBUTES ; INHIBITION ; PROGNOSIS ; CARCINOMA
英文摘要:

Resistance to trastuzumab is a major issue in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Several potential resistance mechanisms have been investigated, but the results are controversial and no conclusion has been reached. Erythropoietin receptor (EPOR) may function in cell growth, and expressed in various cancer cells. Because the downstream signaling pathways for EPOR and HER2 partially overlapped, we hypothesized that EPOR may play a role in the inhibition effect of trastuzumab and resistance to trastuzumab. Here, we detected the expression of EPOR mRNA and protein in HER2-positive breast cancer cell lines and tissues. EPOR expressed in SKBR3, MDA-MB-453, and UACC-812 cell lines, but not in BT474. Of the 55 HER2-positive cancer tissues, EPOR was positive in 42 samples and highly expressed (H-score a parts per thousand yen 25) in 24 by immunohistochemistry. The difference between EPOR expression and Ki67 index was significant (P = 0.033), and EPOR expression also positively correlated with higher pathological stage (Spearman correlation coefficient = 0.359; P = 0.007). Exogenous EPO antagonized trastuzumab-induced inhibition of cell proliferation in HER2/EPOR dual-positive breast cancer cells. We then exposed SKBR3 cells to trastuzumab for 4 months to obtain trastuzumab-resistant SKBR3 cell line, which demonstrated higher phosphorylated EPOR level, higher EPO expression and more extracellular secretion than non-resistant parental SKBR3 cells. Downregulation EPOR expression using short hairpin RNA resensitized trastuzumab-resistant cells to this drug, and SKBR3 cells with EPOR downregulation demonstrated attenuated trastuzumab resistance after the same resistance induction. EPOR downregulation plus trastuzumab produced a synergetic action in the inhibition of cell proliferation and invasion in SKBR3 and MDA-MB-453 cell lines. Therefore, EPOR expression may be involved in tumor progression and proliferation in HER2-positive breast cancer. EPO/EPOR contributes to the mechanism of trastuzumab resistance in SKBR3 cell lines, and EPOR downregulation can reverse the resistance to trastuzumab and increase the inhibition effect of this drug.

语种: 英语
WOS记录号: WOS:000312071000011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57122
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: Peking Univ, Hosp 1, Breast Dis Ctr, Beijing 100871, Peoples R China

Recommended Citation:
Zhang, Chi,Duan, Xuening,Xu, Ling,et al. Erythropoietin receptor expression and its relationship with trastuzumab response and resistance in HER2-positive breast cancer cells[J]. BREAST CANCER RESEARCH AND TREATMENT,2012,136(3):739-748.
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