Biological role of estrogen receptor beta in salivary gland adenocarcinoma cells.

Abstract

This study is intended to investigate the biological role of estrogen receptor (ER) nongenomic signaling in salivary gland adenocarcinoma cells that predominantly express ERbeta. Salivary gland adenocarcinoma cell lines HSG and HSY were used to study the effect of diarylpropionitrile and estrogen on the nongenomic signaling of ERbeta, cytoskeletal remodeling, and cell motility. We found that diarylpropionitrile and estrogen triggered rapid activation of the extracellular signal-regulated kinase 1/2 (ERK), Src, and focal adhesion kinase signaling pathways. Estrogen stimulation also induced long cytoplasmic extensions, filopodia formation, and abnormal outgrowths in both HSG and HSY cells. We further observed that ligand-induced migration of these cells was blocked by the pure antiestrogen ICI 182780 and the mitogen-activated protein/ERK kinase inhibitor PD98059, indicating that estrogen-induced cell migration is mediated by the activation of ERbeta nongenomic signaling. These results clearly showed that ERbeta nongenomic signaling is active in salivary gland cells and has a biological role in migration, presumably via the stimulation of ERK1/2. In future, the findings of this study might have clinical importance as several ERbeta-selective agonists are currently being available, and these could potentially be used for therapeutic targeting of ERbeta-positive salivary tumors.