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 TGFb 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. Ó2012 AACR. IntroductionEpithelial ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer death in women in the Western world (1). Reasons for this high lethality include the late stage at which women are diagnosed and the inherent aggressive biology of this cancer. Largely

T-Type Ca2+ Channel Inhibition Sensitizes Ovarian Cancer to Carboplatin

“…Furthermore, blocking T-type Ca 2+ channels decreased FoxM1 expression. FoxM1 is often overexpressed in ovarian tumors (48), and its transcriptional levels increase with tumor grade, suggesting a role in the progression of ovarian cancer (49). While blocking T-type Ca 2+ channels inhibits PI3K/AKT signaling to FoxO and reduces survivin expression, the direct molecular connection between T-type channels and PI3K/AKT/FoxO pathway is still unknown and likely involves Ca 2+ -dependent pathways.…”

Nidogen 1 and Nuclear Protein 1: novel targets of ETV5 transcription factor involved in endometrial cancer invasion

“…Chromatin immunoprecipitation (ChIP) on HGE cells was performed using rAb ERM/ETV5 and the Magna ChIP kit (Millipore, Billerica, MA), according to the manufacturer's instructions and as previously described in Llaurado et al [13]. Melting temperatures and specific PCR conditions are described in Table 1.…”

“…Immunoblot was performed as described by Llaurado et al [13]. Primary antibodies used in this study were anti-ETV5 (sc-22807, Santa Cruz Biotechnologies, Santa Cruz, CA, USA), anti-NID1 (anti-hNidogen1, MAB2570, R&D Systems, Minneapolis, MN USA), anti-Nupr1 [15] and anti atubulin (2125, Cell Signalling, Danvers, MA).…”

Reversing Platinum Resistance in High-Grade Serous Ovarian Carcinoma: Targeting BRCA and the Homologous Recombination System

“…In breast cancer cells, MYC was found to directly regulate the BRCA1 promoter via binding to distal regulatory regions (55) (Figure 1A). In addition, oncogenic ETS family transcription factors were shown to induce a subset of E2F target genes (56, 57), including BRCA2 (58). Thus, a number of cancer-relevant transcription factors regulate BRCA1 and BRCA2 .…”