IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer
IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer
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DOI：
10.1016/j.cell.2004.07.013
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发表时间：
2004-08-06
期刊：
影响因子：
64.5
通讯作者：
Karin, M
中科院分区：
文献类型：
--
作者：
Greten, FR;Eckmann, L;Karin, M
长期以来人们一直怀疑炎症和癌症之间存在联系，但其分子性质仍然不明确。炎症中的一个关键角色是转录因子 NF-kappaB，其活性是通过 IkappaB 激酶 (IKK) 复合物响应感染因子和促炎细胞因子而触发的。使用结肠炎相关癌症模型，我们发现虽然肠上皮细胞中 IKKbeta 的缺失并不能减少炎症，但它会导致肿瘤发病率急剧下降，而不影响肿瘤大小。这与肿瘤促进过程中上皮细胞凋亡增加有关。然而，删除骨髓细胞中的 IKKbeta 会导致肿瘤大小显着减小。这种缺失减少了可能充当肿瘤生长因子的促炎细胞因子的表达，而不影响细胞凋亡。因此，两种不同细胞类型中 IKK/NF-κB 通路的特异性失活可以减弱炎症相关肿瘤的形成。除了抑制晚期肿瘤的细胞凋亡之外，IKKbeta 还可能将炎症与癌症联系起来。
A link between inflammation and cancer has long been suspected, but its molecular nature remained ill defined. A key player in inflammation is transcription factor NF-kappaB whose activity is triggered in response to infectious agents and proinflammatory cytokines via the IkappaB kinase (IKK) complex. Using a colitis-associated cancer model, we show that although deletion of IKKbeta in intestinal epithelial cells does not decrease inflammation, it leads to a dramatic decrease in tumor incidence without affecting tumor size. This is linked to increased epithelial apoptosis during tumor promotion. Deleting IKKbeta in myeloid cells, however, results in a significant decrease in tumor size. This deletion diminishes expression of proinflammatory cytokines that may serve as tumor growth factors, without affecting apoptosis. Thus, specific inactivation of the IKK/NF-kappaB pathway in two different cell types can attenuate formation of inflammation-associated tumors. In addition to suppressing apoptosis in advanced tumors, IKKbeta may link inflammation to cancer.