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. 17beta Estradiol (E2) was administered to SKOV3 (ERalpha>beta) and DOV13 (ERalpha<ERbeta) 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.
Song
Joon
J
Department of Obstetrics and Gynecology, Yale University, P.O. Box 208063, 333 Cedar Street, FMB 331, New Haven, CT 06520-8063, USA.
Fadiel
Ahmed
A
Edusa
Valentine
V
Chen
Zhaocong
Z
So
John
J
Sakamoto
Hideki
H
Fishman
David A
DA
Naftolin
Frederick
F
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen; D003598:Cytoskeletal Proteins; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin; D010051:Ovarian Neoplasms; D010750:Phosphoproteins / Q000378:metabolism*; D011509:Proteoglycans; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000099149:Ezrin
D003094:Collagen; D003598:Cytoskeletal Proteins; D004338:Drug Combinations; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D007797:Laminin; D010750:Phosphoproteins; D011509:Proteoglycans; D020849:Raloxifene Hydrochloride; D013629:Tamoxifen; D000099149:Ezrin; C059485:matrigel