Studies to identify early markers of ovarian cancer to support the development of chemopreventive regimens have been hindered by the lack of adequate cell models. Using a mouse model of spontaneous transformation, we have isolated mouse ovarian surface epithelial (MOSE) cells from C57BL6 mice and characterized distinct transitional states as they progress from a non-tumorigenic to a highly aggressive malignant phenotype. During neoplastic progression our ovarian cancer model undergoes distinct remodeling of the actin cytoskeleton and focal adhesion complexes, concomitant with downregulation and/or aberrant subcellular localization of two tumor suppressor proteins, E-cadherin and connexin-43. These changes were concurrent with a significant increase in growth rate and anchorage-independent growth capacity. In addition, we demonstrate that epigenetic silencing of the E-cadherin gene via promoter methylation is associated with neoplastic progression of our ovarian cancer model. These results establish critical interactions between cellular cytoskeletal remodeling and epigenetic silencing events in the progression of ovarian cancer. Our novel MOSE model can be used for in vitro and in vivo evaluation of both chemopreventive and chemotherapeutic treatment regimens in the immunocompetent C57BL6 mouse, providing multiple stages and protein markers for treatment efficacy.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]