Tatiana Kisseleva, Li Song, Marina Vorontchikhina, Nikki Feirt, Jan Kitajewski, Christian Schindler
J Clin Invest.
2006;
116(11):2955–2963
doi:10.1172/JCI27392
This article Copyright © 2006, The American Society for Clinical Investigation
Abstract
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Supplemental material
T
he transcription factor NF-κB is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-κB, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-κB in endothelial tissues, Tie2 promoter/enhancer–IκBαS32A/S36A transgenic mice were generated. These mice grew normally but exhibited enhanced sensitivity to LPS-induced toxemia, notable for an increase in vascular permeability and apoptosis. Moreover, B16-BL6 tumors grew significantly more aggressively in transgenic mice, underscoring a new role for NF-κB in the homeostatic response to cancer. Tumor vasculature in transgenic mice was extensive and disorganized. This correlated with a marked loss in tight junction formation and suggests that NF-κB plays an important role in the maintenance of vascular integrity and response to stress.
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