Nuclear hormone receptor NR4A2 is involved in cell transformation and apoptosis
Nuclear hormone receptor NR4A2 is involved in cell transformation and apoptosis
复制标题
DOI：
10.1158/0008-5472.can-04-2134
复制
发表时间：
2004-11-15
期刊：
影响因子：
11.2
通讯作者：
Li, QX
中科院分区：
文献类型：
--
作者：
Ke, N;Claassen, G;Li, QX
HeLaHF 细胞是宫颈癌 HeLa 细胞的转化回复体，失去了贴壁依赖性生长潜力和致瘤性。先前的这种转化逆转涉及肿瘤抑制因子的激活。在这项研究中，进行了表达谱分析，以确定 HeLaHF 细胞中下调的潜在癌基因。我们发现 NR4A1/Nur77/NGFIB 孤儿核激素受体亚家族的所有三个成员（NR4A1、NR4A2 和 NR4A3）在 HeLaHF 回复体中均下调。 HeLa 细胞中小干扰 RNA 介导的 NR4A2 下调，无论是短暂的还是稳定的，都会导致锚定非依赖性生长减少，这在很大程度上归因于失巢凋亡的增加。此外，NR4A2 和 NR4A1 的下调促进了内在细胞凋亡。这些表型也在其他几种实验性癌细胞中观察到，表明观察到的细胞凋亡抑制是 NR4A2 和 NR4A1 更普遍的特性。这些表型还表明孤儿受体的 Nur77/NGFIB 亚家族在细胞增殖和凋亡方面表现出某些致癌功能，因此可以被评估为潜在的癌症治疗靶点。
HeLaHF cells are transformation revertants of cervical cancer HeLa cells and have lost anchorage-independent growth potential and tumorigenicity. Activation of tumor suppressor(s) was implicated previously in this transformation reversion. In this study, expression profiling analysis was carried out to identify potential oncogenes that are down-regulated in HeLaHF cells. We found that all three members of the NR4A1/Nur77/NGFIB orphan nuclear hormone receptor subfamily (NR4A1, NR4A2, and NR4A3) were down-regulated in the HeLaHF revertant. Small interfering RNA-mediated down-regulation of NR4A2 in HeLa cells, either transiently or stably, resulted in reduced anchorage-independent growth that was largely attributable to increased anoikis. Furthermore, downregulation of NR4A2 as well as NR4A1 promoted intrinsic apoptosis. These phenotypes were also observed in several other experimental cancer cells, suggesting the observed apoptosis suppression is a more general property of NR4A2 and NR4A1. These phenotypes also suggest that the Nur77/NGFIB subfamily of orphan receptors exhibit certain oncogenic functionalities with regards to cell proliferation and apoptosis and could therefore be evaluated as potential cancer therapeutic targets.