Multiple signal pathways, such as upregulation of p53 via transcriptional and post-translational modifications, sustained activation of ERK1/2 via GPR30/EGFR signals, and upregulated p21 by p53, ERK1/2, and their cross-talks mediated the in vitro inhibition effects of G-1 on proliferation of ER− breast cancer cells. Here, MAPK3 is linked to breast cancer.