Though both AREG and TGFα are shed and capable of inducing receptor phosphorylation in MDA-231 cells, AREG appears to be the highest cleaved ligand and it is able to potently activate the EGFR on mouse osteoblast-like MC3T3 cells providing the rationale to target this ligand as the main inducer of both autocrine breast cancer signaling and paracrine receptor signaling in mouse tissues. This evidence concerns the gene AREG and breast cancer.