NR4A1 promotes PDGF-BB-induced cell colony formation in soft agar.
NR4A1 promotes PDGF-BB-induced cell colony formation in soft agar.
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DOI：
10.1371/journal.pone.0109047
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Heldin CH
中科院分区：
文献类型：
--
作者：
Eger G;Papadopoulos N;Lennartsson J;Heldin CH
成纤维细胞有丝分裂原血小板衍生生长因子-BB(PDGF-BB)诱导孤儿核受体NR4A1(又称Nur77、TR3或NGFIB)的瞬时表达。本研究的目的是探讨PDGF-BB诱导NR4A1的途径及其功能作用。我们证明在PDGF-BB刺激的NIH3T3细胞中，MEK1/2抑制剂CI-1040强烈抑制NR4A1的表达，而ERK5的下调延迟了NR4A1的表达，但不能阻止它的表达。此外，我们报告了用NF-κB抑制剂BAY11-7082处理抑制NR4A1mRNA和蛋白表达。继续PDGF-BB处理后，NIH3T3中的NR4A1大部分定位于细胞质，仅有一小部分移位到胞核。沉默NR4A1使NIH3T3细胞的增殖率略有增加，但不影响PDGF-BB诱导的趋化或存活能力。此外，过表达NR4A1促进了NIH3T3细胞和胶质母细胞瘤细胞系U-105 MG和U-251 MG的贴壁非贴壁生长。因此，尽管PDGF-BB诱导的NR4A1抑制了细胞在固体表面的生长，但它促进了锚定无关的生长。
The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth.
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