Inflammation Revisited

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Science  03 Sep 2004:
Vol. 305, Issue 5689, pp. 1373
DOI: 10.1126/science.305.5689.1373b

There has been a resurgence of interest in the concept that inflammatory mechanisms can profoundly affect the pathogenesis of many common human diseases. In the case of cancer, much research has focused on the role of NF-κB, a transcription factor that is normally activated in response to pro-inflammatory cytokines and that regulates the expression of more than 200 genes. Many tumor cell lines show constitutive activation of NF-κB signaling, but there has been conflicting evidence as to whether this promotes or inhibits tumorigenesis.

Three groups have studied mouse models of intestinal (Greten et al.), liver (Pikarsky et al.), and mammary (Huber et al.) tumors; they conclude that activation of the NF-κB pathway enhances tumor development and may act primarily in late stages of tumorigenesis. Inhibition of NF-κB signaling uniformly suppressed tumor development but, depending on the model studied, this salutary effect was attributed to an increase in tumor cell apoptosis, reduced expression of tumor cell growth factors supplied by surrounding stromal cells, or abrogation of a tumor cell dedifferentiation program that is critical for tumor invasion/metastasis. Although collectively these results support the development of NF-κB inhibitors as potential anticancer agents, they illustrate that such inhibitors could have complex physiological effects. — PAK

Cell 118, 285 (2004); Nature 10.1038/nature02924 (2004); J. Clin. Invest. 114, 569 (2004).

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