Ezrin Overexpression by Transformed Human Ovarian Surface Epithelial Cells,Ovarian Cleft Cells,and Serous Ovarian Adenocarcinoma Cells

Abstract

Objectives: We have shown that ezrin expression correlates with ovarian epithelial cancer (OVCA) cell proliferation and metastatic behavior. In this study, we evaluated ezrin expression in transformed ovarian superficial epithelial cells (OSE) in ovarian clefts and in culture. Study Design: Immunohistochemistry and Western blotting for immunoreactive ezrin (ir-ezrin) in normal ovarian tissue, cultured OSE, and ovarian epithelial cancer cells. Results: While ir-ezrin was not demonstrable in normal cuboidal surface cells or interior ovarian organelles, cells lining the ovarian clefts strongly expressed ir-ezrin. Long-term culture of OSE increased ezrin expression and cytological abnormalities. Administration of estradiol and insulin at levels reported in inclusions dramatically induced OSE ir-ezrin expression to OVCA levels and membrane specializations; ruffling, pseudopodia and filopodia. Moreover epidermal growth factor (EGF) drastically increased ezrin translocation in OSE cells in a time-dependent manner. Conclusions: Ezrin expression by OSE increases during transformation.  Ezrin expression is responsive to estradiol and growth factors previously shown to be present in ovarian inclusions. These findings suggest that the microenvironment in ovarian inclusions and clefts contributes to the development of OVCA. Our findings elaborate on the mechanism of the ovarian origin of OVCA.