TNF-α upregulates PTEN via NF-κB signaling pathways in human leukemic cells
TNF-α upregulates PTEN via NF-κB signaling pathways in human leukemic cells
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DOI：
10.1038/emm.2007.14
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发表时间：
2007-02-28
影响因子：
12.8
通讯作者：
Kim, Jong-Suk
中科院分区：
文献类型：
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作者：
Lee, Young-Rae;Yu, Hong-Nu;Kim, Jong-Suk
tnf - α具有多种生物学功能，如细胞凋亡、炎症和免疫等。PTEN还具有多种细胞功能，包括细胞生长、增殖、迁移和分化。因此，提出了这两种分子之间可能的关系。已知在人结肠细胞系HT-29中，tnf - α通过NF-kappa B通路下调PTEN。然而，我们在这里展示了相反的发现，tnf - α通过激活人类白血病细胞中的nf - κ B上调PTEN。tnf - α在HL-60细胞中以时间和剂量依赖的方式增加PTEN的表达，但用p65八角糖硫代寡核苷酸或吡咯烷二硫代氨基甲酸酯破坏NF-kappa B可以消除这种反应。我们发现tnf - α激活了nf - κ B通路，在tnf - α处理的细胞中，p65易位到细胞核证明了这一点。我们得出结论，在人白血病细胞中，tnf - α通过活化nf - κ B诱导PTEN表达上调。
TNF-alpha plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between the two molecules are suggested. TNF-alpha has been known to down regulate PTEN via NF-kappa B pathway in the human colon cell line, HT-29. However, here we show the opposite finding that TNF-alpha upregulates PTEN via activation of NF-kappa B in human leukemic cells. TNF-alpha increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of NF-kappa B with p65 anisense phosphorothioate oligonucleotide or pyrrolidine dithiocarbamate. We found that TNF-alpha activated the NF-kappa B pathways, evidenced by the translocation of p65 to the nucleus in TNF-alpha-treated cells. We conclude that TNF-alpha induces upregulation of PTEN expression through NF-kappa B activation in human leukemic cells.