In agreement with the promotive effect of DPAGT1 on HER2 shedding, overexpressing of DPAGT1 drastically impaired the sensitivity of HER2+ breast cancer cells to trastuzumab treatment, as indicated by increased cell viability and colony formation of HER2+ breast cancer cells, as well as the elevated activity of HER2 downstream effector protein kinase B (AKT) and extracellular regulated kinase (ERK1/2) (Figure 2, I and J and Supplemental Figure 2, A and B). This evidence concerns the gene ERBB2 and breast cancer.