Format

Send to

Choose Destination
J Clin Invest. 2006 Nov;116(11):2955-63. Epub 2006 Oct 19.

NF-kappaB regulation of endothelial cell function during LPS-induced toxemia and cancer.

Author information

1
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.

Abstract

The transcription factor NF-kappaB is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-kappaB, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-kappaB in endothelial tissues, Tie2 promoter/enhancer-IkappaBalpha(S32A/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-kappaB 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-kappaB plays an important role in the maintenance of vascular integrity and response to stress.

PMID:
17053836
PMCID:
PMC1616192
DOI:
10.1172/JCI27392
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center