Departments of Obstetrics and Gynecology, The Dan L Duncan Cancer Center, Baylor College of Medicine, The Methodist Hospital, Houston, Texas 77030, USA.
J Clin Endocrinol Metab. 2013 Jul;98(7):E1152-62. doi: 10.1210/jc.2013-1081. Epub 2013 May 20.
Recent evidence implicates the orphan nuclear receptor, nuclear receptor subfamily 2, group F, member 2 (NR2F2; chicken ovalbumin upstream promoter-transcription factor II) as both a master regulator of angiogenesis and an oncogene in prostate and other human cancers.
The objective of the study was to determine whether NR2F2 plays a role in ovarian cancer and dissect its potential mechanisms of action.
DESIGN, SETTING, AND PATIENTS: We examined NR2F2 expression in healthy ovary and ovarian cancers using quantitative PCR and immunohistochemistry. NR2F2 expression was targeted in established ovarian cancer cell lines to assess the impact of dysregulated NR2F2 expression in the epithelial compartment of ovarian cancers.
Our results indicate that NR2F2 is robustly expressed in the stroma of healthy ovary with little or no expression in epithelia lining the ovarian surface, clefts, or crypts. This pattern of NR2F2 expression was markedly disrupted in ovarian cancers, in which decreased levels of stromal expression and ectopic epithelial expression were frequently observed. Ovarian cancers with the most disrupted patterns of NR2F2 were associated with significantly shorter disease-free interval by Kaplan-Meier analysis. Targeting NR2F2 expression in established ovarian cancer cell lines enhanced apoptosis and increased proliferation. In addition, we found that NR2F2 regulates the expression of NEK2, RAI14, and multiple other genes involved in the cell cycle, suggesting potential pathways by which dysregulated expression of NR2F2 impacts ovarian cancer.
These results uncover novel roles for NR2F2 in ovarian cancer and point to a unique scenario in which a single nuclear receptor plays potentially distinct roles in the stromal and epithelial compartments of the same tissue.
最近的证据表明，孤儿核受体 NR2F2（鸡卵清蛋白上游启动子转录因子 II）既是血管生成的主要调节因子，也是前列腺癌和其他人类癌症的癌基因。
本研究旨在确定 NR2F2 是否在卵巢癌中发挥作用，并剖析其潜在的作用机制。
设计、环境和患者：我们使用定量 PCR 和免疫组织化学技术检测了健康卵巢和卵巢癌中 NR2F2 的表达。在已建立的卵巢癌细胞系中靶向 NR2F2 表达，以评估上皮细胞中失调的 NR2F2 表达对卵巢癌的影响。
我们的结果表明，NR2F2 在健康卵巢的基质中强烈表达，在上皮细胞中几乎没有或没有表达，这些上皮细胞排列在卵巢表面、裂隙或隐窝。在卵巢癌中，这种 NR2F2 表达模式明显被打乱，常观察到基质表达减少和上皮异位表达。Kaplan-Meier 分析显示，NR2F2 表达模式最紊乱的卵巢癌患者无病间隔明显缩短。在已建立的卵巢癌细胞系中靶向 NR2F2 表达可增强细胞凋亡并增加增殖。此外，我们发现 NR2F2 调节 NEK2、RAI14 和多个其他参与细胞周期的基因的表达，提示失调的 NR2F2 表达影响卵巢癌的潜在途径。
这些结果揭示了 NR2F2 在卵巢癌中的新作用，并指出了一种独特的情况，即单个核受体在同一组织的基质和上皮细胞中可能发挥不同的作用。
