MTDH mediates trastuzumab resistance in HER2 positive breast cancer by decreasing PTEN expression through an NFκB-dependent pathway.

摘要: Trastuzumab resistance is almost inevitable in the management of human epidermal growth factor receptor (HER) 2 positive breast cancer, which phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss implicated. Since metadherin (MTDH) promotes malignant phenotype we sought to define whether MTDH trastuzumab by decreasing PTEN expression through an NFκB-dependent pathway. The correlations between expressions were analyzed both HER2 cancer tissues resistant SK-BR-3 (SK-BR-3/R) cells. Gene manipulations levels knockdown or overexpression utilized elucidate molecular mechanisms implication resistance. For vivo studies, SK-BR-3/R cells modified derivatives inoculated into nude mice alone under exposure. Tumor volumes, histological examinations as well Ki67 revealed. Elevated indicated poor clinical benefit, shortened progression free survival time, was negatively correlated with level patients restored sensitivity cells, while prevented cell death exposure, probably IκBα inhibition nuclear translocation p65 subsequently decreased expression. Synergized effect regulation observed upon co-transfection. Forced sensitivity. Furthermore, tumor volume increased after subcutaneous xenografts opposite found grafts overexpressing confers cancer. mediates resistance, at least part, pathway, may be a promising therapeutic target for