For instance, carcinoma-associated fibroblasts (CAFs) or mesenchymal stem (stromal) cells (MSCs) can cause ERα-positive breast cancer cells to resist the growth inhibitory effect of anti-estrogens by causing these cells to activate the PI3K (phosphoinositol-3-kinase)/AKT-signaling pathway by inducing downregulation of the IGF (insulin-like growth factor)-regulating protein IGFBP5 (IGF binding protein 5) [10]. This evidence concerns the gene ESR1 and breast cancer.