Cross-talk between ER and HER2 regulates c-MYC-mediated glutamine metabolism in aromatase inhibitor resistant breast cancer cells

被引：71

作者：

Chen, Zhike ^{[1
]}

Wang, Yuanzhong ^{[1
]}

Warden, Charles ^{[2
]}

Chen, Shiuan ^{[1
]}

机构：

[1] City Hope Natl Med Ctr, Dept Canc Biol, Beckman Res Inst, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Dept Mol Med, Beckman Res Inst, Bioinformat Core, Duarte, CA 91010 USA

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2015年 / 149卷

基金：

美国国家卫生研究院;

关键词：

c-MYC; ER; HERZ; Glutamine; Aromatase inhibitor resistance; Breast cancer; ESTROGEN-RECEPTOR; GENE-EXPRESSION; ACTIVATION; OVEREXPRESSION; PATHWAYS; THERAPY; GLUCOSE; GROWTH;

D O I：

10.1016/j.jsbmb.2015.02.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer is a significant clinical problem for a considerable number of patients. The oncogenic transcription factor c-MYC (hereafter referred to as MYC), which regulates glutamine metabolism in cancer cells, has been linked to endocrine resistance. We were interested in whether MYC-mediated glutamine metabolism is also associated with aromatase inhibitor (AI) resistant breast cancer. We studied the expression and regulation of MYC and the effects of inhibition of MYC expression in both AI sensitive and resistant breast cancer cells. Considering the role of MYC in glutamine metabolism, we evaluated the contribution of glutamine to the proliferation of AI sensitive and resistant cells, and performed RNA-sequencing to investigate mechanisms of MYC-mediated glutamine utilization in AI resistance. We found that glutamine metabolism was independent of estrogen but still required estrogen receptor (ER) in AI resistant breast cancer cells. The expression of ANC oncogene was up-regulated through the cross-talk between ER and human epidermal growth factor receptor 2 (HER2) in AI resistant breast cancer cells. Moreover, the glutamine transporter solute carrier family (SLC) 1A5 was significantly up-regulated in AI resistant breast cancer cells. ER down-regulator fulvestrant inhibited MYC, SLC1A5, glutaminase (GLS) and glutamine consumption in AI resistant breast cancer cells. Inhibition of MYC, SLC1A5 and GLS decreased AI resistant breast cancer cell proliferation. Our study has uncovered that MYC expression is up-regulated by the cross-talk between ER and HER2 in AI resistant breast cancer cells. MYC-mediated glutamine metabolism is associated with AI resistance of breast cancer. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：118 / 127

页数：10

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