miR-126-mediated activation of IGF2/IGF1R/IRS1 signaling promotes the Herceptin resistance in ErbB2 positive breast cancer cells
10.3760/cma.j.issn.1008-1372.2017.02.002
- VernacularTitle:miR-126介导的IGF2/IGF1R/IRS1信号活化促进ErbB2阳性乳腺癌细胞对Herceptin的耐受
- Author:
Liyun LUO
;
Xiaoting JIA
;
Guopei ZHENG
;
Zhimin HE
- Keywords:
MicroRNAs;
Insulin-like growth factor Ⅱ;
Receptor,IGF type 1;
Receptor,insulin;
Breast neoplasms/DT/ME;
Drug tolerance;
Antibodies,monoclonal/TU
- From:
Journal of Chinese Physician
2017;19(2):163-167
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of insulin-like growth factor-2/insulin-like growth factor1 receptor/insulin receptor substrate-1 (IGF2/IGF1R/IRS1) signal pathway inducing the chemoresistance of epidermal growth factor receptor 2 (ErbB2) positive breast cancer cells to Herceptin.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay were used to determine the expression levels of IGF2,IGF1 R,and IRS1.The direct targets of miR-126 were validated by dual-luciferase reporter gene assay.In SKBR3/pool2 cells,IGF1 R activity was reduced by an inhibitor of IGF1 R,and IRS1 was knocked-down by shRNAs.Furthermore,3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was performed to evaluate the sensitivity of these treated cells to Herceptin.Results IGF2,IGF1 R,and IRS1 were significantly higher expressed in SKBR3/pool2 cell compared to that in SKBR3 cell.Western blot assay showed that IGF2/IGF1R/IRS1 was activated in SKBR3/pool2 cells.Bioinformatics analysis combined with luciferase activity suggested that miR-126 directly targeted IRS1.MTS results demonstrated that the chemosensitivity to Herceptin of SKBR3/ pool2 cells with inhibitor of IGF1R or shRNAs targeting IRS1 or overexpressing miR-126 was significantly reduced.Conclusions IGF2/IGF1R/IRS1 signal pathway confers to the chemoresistance of ErbB2 positive breast cancer cells to Herceptin.
