Role of Smad proteins in the regulation of NF-κB by TGF-β in colon cancer cells
Role of Smad proteins in the regulation of NF-κB by TGF-β in colon cancer cells
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DOI：
10.1016/j.cellsig.2005.08.021
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发表时间：
2006-07-01
影响因子：
4.8
通讯作者：
Beauchamp, RD
中科院分区：
文献类型：
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作者：
Grau, AM;Datta, PK;Beauchamp, RD
核因子κ B（NF-κ B）与癌细胞存活有关。我们探讨了TGF-β通路在结肠癌细胞NF-κ B调节中的作用。结肠腺癌细胞系FET-1的TGF-β-1处理导致NF-κ B核转位和DNA结合活性之前的I κ B-α磷酸化的所有早期增加。TGF-β I型受体的活化是TGF-β介导的NF-κ B活化所必需的。在Smad4无效细胞系SW 480中没有观察到NF-κ B的活化，即使TGF-β确实导致I κ B-α。这些细胞中的磷酸化。Smad4恢复TGF-β 1介导的NF-κ B活化在表达抑制性Smad、Smad 7的FET-1细胞中，TGF-β-1处理未能激活NF-κ B或磷酸化I κ B-α。综上所述，这些结果表明Smad4在NF-κ B B的转录激活中的作用，以及Smad7抑制I κ B-α磷酸化的直接作用，而不是通过充分确立的抑制Smad2/3磷酸化随后抑制TGF-β途径。(c)2005年爱思唯尔公司All rights reserved.
Nuclear factor kappa B (NF-kappa B) has been implicated in cancer cell survival. We explored the role of the TGF-beta pathway in the regulation of NF-kappa B in colon cancer cells. TGF-beta-1 treatment of the colon adenocarcinoma cell line FET-1, results in ail early increase in I kappa B-alpha phosphorylation that precedes NF-kappa B nuclear translocation and DNA binding activity. Activation of the TGF-beta type I receptor is required for the TGF-beta-mediated activation of NF-kappa B. No activation of NF-kappa B is observed in a Smad4 null cell line, SW480, even though TGF-beta does result in I kappa B-alpha. phosphorylation in these cells. Smad4 restores the TGF-beta-1-mediatcd NF-kappa B activation in SW480 cells. TGF-beta-1 treatment fails to activate NF-kappa B or phosphorylate I kappa B-alpha in FET-1 cells expressing the inhibitory Smad, Smad7. Taken together, these results suggest a role for Smad4 in the transcriptional activation of NF-kappa B, and a direct effect of Smad7 inhibiting I kappa B-alpha phosphorylation rather than through the well-established inhibition of Smad2/3 phosphorylation with subsequent inhibition of the TGF-beta pathway. (c) 2005 Elsevier Inc. All rights reserved.