ESR1 and breast cancer: Ali et al. (2010, 2012) ruled out classical ER signaling through ERE-regulated genes in Cd-induced estrogenic responses observed in vivo and observed that activation of MAPK pathways was a mode of action for Cd. Liu et al. (2008) suggested that rapid activation of ERK1/2 and AKT in human breast cancer cell lines may occur through membrane ERα and GPR30, suggesting the presence of crosstalk between hormone and growth factor signaling pathways involved in Cd-induced cell signaling.