The function and mechanism of ErbB3 and IGF1R in breast cancer with Herceptin resistance / 中国医师杂志

ABSTRACT

Objective To investigate the role of epidermal growth factor receptor 3 (ErbB3) and insulin-like growth factor-1 receptor (IGF1R) in enhancing the resistance of Herceptin in human breast cancer.Methods HRG (Heregulin,the ligand of ErbB3) or IGF2 (insulin-like growth factor2,the ligand of IGF1R) was correspondingly added into breast cancer cells SKBR3 and BT474,and then 3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and were performed in these cells to evaluate the sensitivity of these cells to Herceptin.Furthermore,we used HRG or IGF2 antibodies to inhibit their joint receptors in Herceptin-resistant breast cancer cells SKBR3/POOL2 and BT474/HR20.Finally,the sensitivity of these treated cells to Herceptin was detected via MTS assay.HRG or IGF2 was added into breast cancer cell BT474,and co-IP assay was used to detect the expressions of ErbB3 and IGF1R which combined with ErbB2.Results The treatment groups used HRG or IGF2 enhanced the resistance of Herceptin in Herceptin-sensitive breast cancer cells.On the other hand,we used antibodies of HRG and IGF2 to block their combining with their receptors in Herceptin-resistant breast cancer cells,the cells became more sensitive to Herceptin.BT474 cell was treated with HRG or IGF2.The expressions of ErbB3 and IGF1R which combined with ErbB2 were increased.Conclusions The formation of heterodimers ErbB2/ErbB3 and ErbB2/IGF1R might enhance the resistance of Herceptin in ErbB2-overexpression human breast cancers.