Analysis of Gene Expression Regulated by the ETV5 Transcription Factor in OV90 Ovarian Cancer Cells Identifies FOXM1 Overexpression in Ovarian Cancer

Abstract

Epithelial ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer death in women in the Western world. ETS transcription factors have been implicated in the regulation of gene expression during a variety of biologic processes including cell growth and differentiation. We recently examined the role of the ETS transcription factor ETV5 in epithelial ovarian cancer and described ETV5 as being upregulated in ovarian tumor samples as compared with ovarian tissue controls. In ovarian cancer cells, we showed that ETV5 regulated the expression of cell adhesion molecules, enhancing ovarian cancer cell survival in anchorage-independent conditions and suggesting that it plays a role in ovarian cancer cell dissemination and metastasis into the peritoneal cavity. To understand the role of ETV5 transcription factor during ovarian cancer cell dissemination, we analyzed by gene expression microarray technology those genes whose expression was altered in an ovarian cancer cell line with a stable downregulation of ETV5. The analysis of the genes and signaling pathways under the control of ETV5 in OV90 cells has unraveled new signaling pathways that interact with ETV5, among them the cell-cycle progression and the TGFβ signaling pathway. In addition, we found that the downregulation of ETV5 reduced the expression of the oncogenic transcription factor FOXM1. Consistently, FOXM1 was overexpressed in ovarian tumor samples, and its transcriptional levels increased with ETV5 transcription in ovarian tumor samples. Moreover, FOXM1 expression levels increased with tumor grade, suggesting a role in the progression of ovarian cancer. Mol Cancer Res; 10(7); 914–24. ©2012 AACR.