Estrogen regulates PTEN to induce epithelial ovarian cancer cell proliferation using a two-pronged approach: genomic pathway and non-genomic pathway

Background: Epithelial ovarian cancer (EOC) has the highest mortality rate among malignant tumors in women and its occurrence and development are strongly linked to estrogen. Having identified the phosphatase and tensin homologue (PTEN) is a potent tumor suppressor regulating cell proliferation, migration, and survival. Although the role of PTEN in inhibiting cancer has long been emphasized, the role in estrogen-induced EOC is unclear. Results We got the following main results. (1) PTEN expression is decreased in EOC tissues. (2) Estrogen decreased PTEN expression in EOC cells via the estrogen receptor ESR1. (3) Knockdown of PTEN enhanced the proliferation and migration of SK-OV-3 cells by estrogen. (4) Estrogen induced phosphorylation of PTEN via the G-protein-coupled receptor (GPCR)-Protein kinase C (PKC) non-genomic pathway. (5) Inhibiting the phosphorylation of PTEN weakened the proliferation and migration of SK-OV-3 cells by estrogen and decreased the phosphorylation of AKT and mammalian target of rapamycin (mTOR). Conclusion The data indicated that estrogen decreased PTEN expression level via the ESR1 genomic pathway and phosphorylated PTEN via the GPCR-PKC non-genomic pathway to activate the PI3K/AKT/mTOR signaling pathway, thereby determining the fate of epithelial ovarian cancer cells.