In contrast, stimulation of SKBR3 cells with epidermal growth factor or heregulin β1 (HRGβ1) upregulates RARα expression [40], yet resistance to atRA-induced growth inhibition has been reported for HER2-overexpressing breast cancer cells (either HER2-transfected MCF7 cells or naturally overexpressing BT474 or MDA-MB-453 cells); pretreatment for several days with trastuzumab could sensitize these latter two cell lines to inhibition by atRA [41,42]. The gene discussed is ERBB2; the disease is breast cancer.