Daintain/AIF-1 promotes breast cancer proliferation via activation of the NF-κB/cyclin D1 pathway and facilitates tumor growth
Daintain/AIF-1 promotes breast cancer proliferation via activation of the NF-κB/cyclin D1 pathway and facilitates tumor growth
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DOI：
10.1111/j.1349-7006.2008.00787.x
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发表时间：
2008-05-01
期刊：
影响因子：
5.7
通讯作者：
Chen, Zheng-Wang
中科院分区：
文献类型：
--
作者：
Liu, Shou;Tan, Wen-Yong;Chen, Zheng-Wang
最近的研究表明，炎症因子在包括乳腺癌在内的癌症的发生和发展中起着重要作用。Daintain/allograft inflammatory factor-1 （AIF-1）在炎症反应中起着至关重要的调节作用，但目前还没有报道Daintain/ AIF-1是否参与乳腺癌的发生。本研究通过免疫组化分析发现，daintain/AIF-1在乳腺导管肿瘤上皮中呈强阳性表达，而在相邻组织学正常的导管上皮中仅呈弱阳性或阴性表达。然后，通过将daintian/AIF-1基因转导到细胞中，并通过短干扰RNA抑制daintian/AIF-1的表达，探讨daintian/AIF-1对乳腺癌细胞株MDA-MB-231增殖的影响。结果表明，上调和下调daintain/AIF-1表达分别促进和抑制MDA-MB-231的增殖。更有趣的是，daintain/AIF-1过表达促进了雌性裸鼠的肿瘤生长。此外，我们发现daintain/AIF-1过表达上调了cyclin D1的表达，并增强了cyclin D1表达的调节因子NF-kappa B的转录活性。而下调daintain/AIF-1表达可降低cyclin D1的表达，抑制NF-kappa B的转录活性。这些结果强烈提示，daintain/AIF-1可通过激活NF-kappa B信号通路促进乳腺肿瘤的生长，进而上调cyclin D1的表达，提示daintain/AIF-1可能成为乳腺癌预后和治疗的新靶点分子。
Recent research indicates that inflammatory factors play important roles in the initiation and progression of cancers, including breast cancer. Daintain/allograft inflammatory factor-1 (AIF-1) is a crucial mediator in the inflammatory response, but it has not yet been reported whether daintain/AIF-1 is involved in the development of breast cancers. In this study, immunohistochemical analysis found strong positive expression of daintain/AIF-1 in breast ductal tumor epithelia, but only weakly positive or negative expression in the adjacent histologically normal ductal epithelia. Then, the effect of daintian/AIF-1 on the proliferation of the breast cancer cell line MDA-MB-231 was explored via transduction of the daintian/AIF-1 gene into the cells, and via inhibition of the expression of daintain/AIF-1 through short interference RNA. The results demonstrated that up-regulation and down-regulation of daintain/AIF-1 expressions promoted and inhibited the proliferation of MDA-MB-231, respectively. More interestingly, daintain/AIF-1 overexpression facilitated tumor growth in female nude mice. Furthermore, we found that daintain/AIF-1 overexpression up-regulated the expression of cyclin D1 and enhanced the transcriptional activity of nuclear factor-kappa B (NF-kappa B), a regulator of cyclin D1 expression. In contrast, the down-regulation of daintain/AIF-1 expression decreased cyclin D1 expression and inhibited the transcriptional activity of NF-kappa B. These results strongly suggest that daintain/AIF-1 can promote the growth of breast tumors via activating NF-kappa B signaling, which consequently up-regulates the expression of cyclin D1, implying that daintain/AIF-1 may be a novel target molecule for the prognosis and therapy of breast cancer.