Linked Life Data

16407217

Source:http://linkedlifedata.com/resource/pubmed/id/16407217

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2006-3-27
pubmed:abstractText
Epithelial cells undergo a form of apoptosis termed anoikis when they lose extracellular attachments. We evaluated the role of transcription factor NF-kappaB in the regulation of anoikis susceptibility of intestinal epithelial cells. Culture of rat intestinal epithelial cells in suspension induced NF-kappaB activation, which blocked the anoikis of those cells, as assessed by internucleosomal DNA fragmentation and caspase-3 cleavage. Activation of NF-kappaB after the loss of extracellular attachments required focal adhesion kinase tyrosine 397 phosphorylation. This triggered a signaling cascade through phosphatidylinositol 3-kinase and AKT, to induce DNA binding of the RelA/p65 NF-kappaB polypeptide. NF-kappaB activated in this manner induced the up-regulated expression of a distinct program of genes that included osteoprotegerin, BCL-2, and IAP-1 (inhibitor of apoptosis protein-1). Chromatin immunoprecipitation experiments revealed that NF-kappaB directly regulated the promoters of these 3 genes. Knock-down of the expression of osteoprotegerin, BCL-2, or inhibitor of apoptosis protein-1 by RNA interference showed that these factors inhibit anoikis, and genetic reconstitution of their expression alone or in combination restored normal levels of anoikis to NF-kappaB-inactive intestinal epithelial cells. Together, these findings have identified the molecular components of a previously unrecognized antianoikis pathway in intestinal epithelial cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8686-96
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16407217-Animals, pubmed-meshheading:16407217-Anoikis, pubmed-meshheading:16407217-Cell Culture Techniques, pubmed-meshheading:16407217-Cell Line, pubmed-meshheading:16407217-Chromatin Immunoprecipitation, pubmed-meshheading:16407217-Electrophoretic Mobility Shift Assay, pubmed-meshheading:16407217-Gene Expression Regulation, pubmed-meshheading:16407217-Glycoproteins, pubmed-meshheading:16407217-Inhibitor of Apoptosis Proteins, pubmed-meshheading:16407217-NF-kappa B, pubmed-meshheading:16407217-Osteoprotegerin, pubmed-meshheading:16407217-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:16407217-RNA, Small Interfering, pubmed-meshheading:16407217-RNA Interference, pubmed-meshheading:16407217-Rats, pubmed-meshheading:16407217-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:16407217-Receptors, Tumor Necrosis Factor, pubmed-meshheading:16407217-Up-Regulation
pubmed:year
2006
pubmed:articleTitle
Antianoikis effect of nuclear factor-kappaB through up-regulated expression of osteoprotegerin, BCL-2, and IAP-1.
pubmed:affiliation
Gastroenterology Research Unit and Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural