| Loss of Ikkbeta promotes migration and proliferation of mouse embryo fibroblast cells. | |
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MedLine Citation:
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PMID: 16966325 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The IkappaB kinase complex (IKK) is central to the activation of NF-kappaB, a critical transcription factor governing expression of genes involved in cell proliferation and anti-apoptotic responses. Mice with genetic disruptions of the Ikkbeta or Ikkgamma gene loci die during embryogenesis because of severe hepatic apoptosis. We now show that Ikkbeta gene deficiency promotes migration and proliferation of mouse embryo fibroblast cells. Morphological analyses revealed an unusual protrusion of the cytoplasm in Ikkbeta(-/-) cells when cultured at a lower density. In a Boyden chamber assay, Ikkbeta(-/-) cells exhibited a high rate of invasion and migration. Enhanced formation of actin stress fibers was also observed in the Ikkbeta(-/-) cells. Mechanistic studies indicated that IKKbeta affects the expression of proteins involved in the assembly of cytoskeleton and cell movement. Furthermore, re-expression of Ikkbeta and antioxidant treatment in Ikkbeta(-/-) cells caused a reversal of protrusive phenotype and high motility, respectively. Furthermore, elimination of reactive oxygen species (ROS) blocked expression of snail and subsequently derepressed E-cadherin expression. Although the underlying mechanism is likely entangled and complicated, the data presented indicate that generation of ROS played a key role in the morphological and mobility changes in Ikkbeta(-/-) cells. These data thus suggest that IKKbeta provides inhibitory signals for cell mobility and growth. Deficiency in the Ikkbeta gene promotes cell mobilization, at least partially, through a ROS-dependent mechanism. |
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Authors:
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Fei Chen; Yongju Lu; Vince Castranova; Zhiwei Li; Michael Karin |
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Publication Detail:
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Type: Journal Article Date: 2006-09-11 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 281 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-11-27 Completed Date: 2007-01-30 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 37142-9 Citation Subset: IM |
Affiliation:
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Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. lfd3@cdc.gov |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / pharmacology Apoptosis Cell Adhesion Cell Movement Cell Proliferation Embryo, Mammalian / cytology* Epithelial Cells / metabolism Fibroblasts / metabolism* Gene Expression Regulation* Humans I-kappa B Kinase / metabolism, physiology* Mice Phenotype RNA Interference Reactive Oxygen Species |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Reactive Oxygen Species; EC 2.7.11.10/I-kappa B Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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