MAPK3 and breast cancer: Because activated GPR30 at the cell membrane promotes HB-EGF release to activate the EGFR signaling pathway, resulting in phosphorylation of Erk1/2 in breast cancer cells, and TAM-R cells (as described above) increase activation of Erk1/2 in response to E2, G1 and Tam, the effect of GPR30 on EGFR signaling was tested in TAM-R cells.