Abstract
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. 17β Estradiol (E 2) was administered to SKOV3 (ERα>β) and DOV13 (ERα<ERβ) 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.
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