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

Song, Joon; Fadiel, Ahmed; Edusa, Valentine; Chen, Zhaocong; So, John; Sakamoto, Hideki; Fishman, David A.; Naftolin, Frederick

doi:10.1016/j.canlet.2004.04.024

Next »Cancer Letters
Volume 220, Issue 1 , Pages 57-65, 18 March 2005

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

Joon Song
- Department of Obstetrics and Gynecology, Yale University, P.O. Box 208063, 333 Cedar Street, FMB 331, New Haven, CT 06520-8063, USA
Ahmed Fadiel
- Department of Obstetrics and Gynecology, Yale University, P.O. Box 208063, 333 Cedar Street, FMB 331, New Haven, CT 06520-8063, USA
Valentine Edusa
- Department of Obstetrics and Gynecology, Yale University, P.O. Box 208063, 333 Cedar Street, FMB 331, New Haven, CT 06520-8063, USA
Zhaocong Chen
- Department of Obstetrics and Gynecology, Yale University, P.O. Box 208063, 333 Cedar Street, FMB 331, New Haven, CT 06520-8063, USA
John So
- Department of Obstetrics and Gynecology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
- Tel.: +1-212-263-7141.
Hideki Sakamoto
- Department of Obstetrics and Gynecology, Faculty of Medicine, Nihon University, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173, Japan
- Tel.: +81-3-3972-8111.
David A. Fishman
- Department of Obstetrics and Gynecology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
- Tel.: +1-212-263-7141.
Frederick Naftolin
- Department of Obstetrics and Gynecology, Yale University, P.O. Box 208063, 333 Cedar Street, FMB 331, New Haven, CT 06520-8063, USA
- Corresponding author. Tel.: +1-203-785-4003; fax: +1-203-785-5294.

Received 25 September 2003; received in revised form 14 January 2004; accepted 3 April 2004.

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 (E₂) 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. E₂ 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 E₂. Increases in cell number and ezrin expression were confirmed by flask incubations. E₂ stimulation of OVCA cell proliferation, motility and Matrigel penetration was dose-related and raloxifene or tamoxifen blocked E₂'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.

Keywords: Ovarian cancer, Estrogen, Ezrin, Gene expression, Metastasis