Global transcriptomic analysis reveals CYP1A1 as a target of the GPER agonist G1

Background : G1, a G-protein coupled estrogen receptor (GPER) agonist, has been instrumental in delineating the mechanisms and cellular consequences of GPER signal transduction. The effects of G1 on cell proliferation are controversial, including those that are demonstrably GPER-independent. It begs the question as to whether G1 has off-target effects. Methods and Results : Here, transcriptomic alterations in MCF-7 breast cancer cells treated with 1 mM G1 are presented. GSEA and GO analysis showed enrichment of gene-sets in G1-treated MCF-7 transcriptome, which align with loss of cell viability. Genes related to xenobiotic metabolism were regulated by G1. In this category, CYP1A1, was the topmost G1-induced gene. CH223191, an aryl hydrocarbon receptor inhibitor, blocked G1-mediated increase in CYP1A1 mRNA. Furthermore, the G1-mediated modulation of CYP1A1, and other genes, was also observed in the GPER-negative MDA-MB-453 cells. Conclusions : This study captures the transcriptomic alterations associated with G1-induced cell cycle arrest in MCF-7 cells, with the important caveat that these may not be entirely attributed to GPER activation.