Estrogen receptor α phosphorylated at Ser167: Distribution and prognostic implications in endometrial cancer.

Abstract

e15539 Background: Both ligand-dependent and ligand-independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation, which is enhanced by ligand binding. Similar to Akt, ERα is activated through phosphorylation at Ser167, resulting in activation of the ERα-dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and mitogen-activated protein kinase (MAPK)/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated- (p-) ERα. The purpose of this study was to determine the importance of Ser167 phosphorylation in EEC progression. Methods: Immunohistochemical staining of primary EEC surgical specimens (n=103) was carried out using antibodies specific for p-ERα and for p-Akt, p-mTOR/S6K1 and p-MAPK/RSK. and for p-Akt, p-mTOR/S6K1 and p-MAPK/RSK. Results: Patients positive for nuclear Ser167 phosphorylation had significantly shorter relapse free survival. Althoughthe result was not significant, levels of nuclear p- tended to be higher in advanced-stage ECC patients. Nuclear p-ERα was significantly positively correlated with p-MAPK and p-S6K1. Conclusions: The amount of nuclear ERa Ser167 phosphorylation is associated with p-MAPK and p-S6K1, and may be important in EEC progression and outcome.