Heregulin-尾1-induced GPR30 upregulation promotes the migration and invasion potential of SkBr3 breast cancer cells via ErbB2/ErbB3-MAPK/ERK pathway

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• 作者：Shu-Qin Ruan^a ; Zhan-Huai Wang^a ; Shan-Wei Wang^b ; Zhi-Xuan Fu^a ; Kan-Lun Xu^b ; Dong-Bo Li^c ; Su-Zhan Zhang^a ; ^{suzhanzhang@gmail.com}
• 关键词：GPR30 ; G protein-coupled receptor 30 ; TAM ; tamoxifen ; GPCR ; G protein-coupled receptor ; E2 ; 17-尾-estradiol ; 4-OHT ; 4-hydroxy-tamoxifen ; HRG ; heregulin ; ER ; estrogen receptor ; EGFR ; epidermal growth factor receptor ; EGF ; epidermal growth factor ; TGF ; tran
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：6 April, 2012
• 卷：420
• 期：2
• 页码：385-390
• 文件大小：570 K

摘要

Estrogen receptor (ER)-negative breast cancer cells are probably more aggressive with larger metastatic potential than ER-positive cells. Loss of ER in recurrent breast cancer is associated with poor response to endocrine therapy. G protein-coupled receptor 30 (GPR30) is expressed in half of ER-negative breast cancers. Tumor cell-derived heregulin-尾1 (HRG-尾1) is also found mainly in ER-negative cancer. In SkBr3 breast cancer cells that lack ER but express GPR30, HRG-尾1 upregulates mRNA and protein levels of GPR30 by promoting ErbB2-ErbB3 heterodimerization and activating the downstream MAPK-ERK signaling pathway. Moreover, GPR30 boosts HRG-尾1-induced migration and invasion of SkBr3 cells after combinative treatment with E2, 4-hydroxy-tamoxifen or the specific GPR30 agonist G-1, which are blocked by the specific GPR30 antagonist G-15 or the transfection with the small interfering RNA for GPR30. The ErbB2 inhibitor AG825 and the MEK1/2 inhibitor U0126 also partly inhibit the enhanced migration and invasion. Therefore, HRG-尾1-induced migration and invasion partly depend on the upregulation of GPR30 expression through activation of the ErbB2-ERK pathway in SkBr3 cells. The results of this study indicate that the crosstalk between GPR30 and HRGs signaling is important for endocrine therapy resistance and may provide a new therapeutic way to treat breast cancer.