Fig. 1

Integrin α11 overexpression induces resistance to anticancer drugs in breast cancer cells

(A) Differential gene expression analysis was conducted using Nanostring nCounter Pancancer Pathway array kits, and the results were visualized as a Venn diagram. (B, C) The 117 genes commonly up-regulated in TAMR and ADR compared to parental MCF-7 cells are shown as heatmaps (B) and functionally enriched Gene Ontology (GO) pathways (fold change ≥ 2, p < 0.05) (C). (D) Gene Set Enrichment Analysis (GSEA) of transcriptome data was performed on TAMR and ADR cells. (E-G) Transfection of TAMR and ADR cells with ITGA11 siRNA recovers sensitivity to tamoxifen or Doxorubicin: Cell viability by MTT assay (E), FACS analysis showing early and late apoptosis (F), and caspase-3 activity (G) in ITGA11 siRNA-transfected TAMR and ADR cells in the presence of different concentrations of tamoxifen or Doxorubicin. *p < 0.05, compared to siNT-transfected group. ^#p < 0.05 compared to siRNA and vehicle-treated group. (H) Western blot analysis shows the expression of Integrin α11 and integrin β1 at basal level of MCF-7, TAMR, and ADR cells. (I) Western blots of immunoprecipitates (IP) with an anti-integrin α11 antibody show that integrin α11 interacts with integrin β1. IgG was used as a negative control antibody. ‘In’ represents input (the total protein lysate used). (J) TAMR and ADR cells transfected with ITGB1 siRNA were analysed for recovery of sensitivity to tamoxifen and Doxorubicin