Estradiol-induced ezrin overexpression in ovarian cancer: a new signaling domain for estrogen

We have for the first time exposed estrogen's role in the epithelial ovarian cancer (OVCA) metastatic cascade and discovered that it is related to the induction of ezrin over-expression. 170 Estradiol (E-2) was administered to SKOV3 (ER alpha >beta) and DOV13 (ER alpha < ER beta) OVCA cells in serum-and phenol red-free medium fortified with transferrin and insulin. Incubated cells that penetrated Matrigel membranes were counted, immunostained and analyzed for immunoreactive ezrin. E-2 induced an invasive phenotype with translocation of ezrin to cell edges, including pseudopodia and ruffles. A strong correlation was found between ezrin expression and Matrigel penetration induced by E-2. Increases in cell number and ezrin expression were confirmed by flask incubations. E-2 stimulation of OVCA cell proliferation, motility and Matrigel penetration was dose-related and raloxifene or tamoxifen blocked E-2's effect, supporting an ER action. This previously unreported effect of estrogen on ezrin expression may play a role in the clinical course of estrogen-sensitive cancers and other normal or diseased cell actions. (c) 2004 Elsevier Ireland Ltd. All rights reserved.