Tamoxifen resistance in breast cancer elucidating mechanisms
CAF8,18-CM induced resistance to tamoxifen in MCF7 cells compared with control or NAF-CM based on both cell viability (Figure 2a) and colony formation assays (Figure 2c).
Moreover, tamoxifen treatment inhibited tumor growth only in the group of MCF7 cells mixed with NAF, but not in mixed CAF group (Supplementary Figure 1).However, the mechanisms underlying the role that cancer-associated fibroblasts (CAFs) have in the development of tamoxifen resistance in luminal Br CA are unclear.The current study was designed to determine if and how CAFs contribute to the development of tamoxifen resistance in Br CA.We demonstrate that CAFs downregulate ER-α expression through secretion of IL-6 that leads to degradation of ER-α.
These results suggest that targeting IL-6 or its downstream targets could serve as an effective therapeutic strategy for luminal Br CA.
Response to different concentrations of tamoxifen after culture of MCF7 and T47D cells with conditioned media from CAFs and NAFs.