Loss of IkkB Promotes Migration and Proliferation of Mouse Embryo Fibroblast Cells

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Karin M ; Li Z ; Lu Y
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Free Radicals Genetics Laboratories Mutagens Occupational Health Safety
• Keywords:
  Animal-studies Antioxidation Free-radical-generation Free-radicals Genes Laboratory-animals Mutation
• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  281
• Issue:
  48
• NIOSHTIC Number:
  nn:20031275
• Citation:
  J Biol Chem 2006 Dec; 281(48):37142-37149
• Contact Point Address:
  PPRB/NIOSH, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  lfd3@cdc.gov
• Federal Fiscal Year:
  2007
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:336c9aeb6be270ea765fe3c774b491b2183599035351f43436b0ad29461d32d7215f8a7e8971b4476c90d676f528e1726eaa2e4d3fb95504131705923e4b977f
• Download URL:
  https://stacks.cdc.gov/view/cdc/191572/cdc_191572_DS1.pdf
• File Type:
  [PDF - 677.92 KB ]