Research Unit in Biomedicine and Translational and Pediatrics Oncology, Hospital Universitari Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
Mol Cancer Res. 2012 Jul;10(7):914-24. doi: 10.1158/1541-7786.MCR-11-0449. Epub 2012 May 15.
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.
上皮性卵巢癌是最致命的妇科恶性肿瘤，也是西方世界女性癌症死亡的第五大主要原因。ETS 转录因子在多种生物学过程的基因表达调控中发挥作用，包括细胞生长和分化。我们最近研究了 ETS 转录因子 ETV5 在卵巢上皮性癌中的作用，并描述了 ETV5 在卵巢肿瘤样本中与卵巢组织对照相比上调。在卵巢癌细胞中，我们表明 ETV5 调节细胞黏附分子的表达，增强卵巢癌细胞在无锚定条件下的存活能力，提示它在卵巢癌细胞扩散和转移到腹腔中发挥作用。为了了解 ETV5 转录因子在卵巢癌细胞扩散过程中的作用，我们通过基因表达微阵列技术分析了在 ETV5 稳定下调的卵巢癌细胞系中表达改变的那些基因。对 OV90 细胞中受 ETV5 调控的基因和信号通路的分析揭示了与 ETV5 相互作用的新信号通路，其中包括细胞周期进展和 TGFβ 信号通路。此外，我们发现 ETV5 的下调降低了致癌转录因子 FOXM1 的表达。一致地，FOXM1 在卵巢肿瘤样本中过度表达，并且其转录水平随卵巢肿瘤样本中 ETV5 的转录而增加。此外，FOXM1 的表达水平随肿瘤分级而增加，提示其在卵巢癌进展中发挥作用。
