Linked Life Data

15989949

Source:http://linkedlifedata.com/resource/pubmed/id/15989949

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-7-1
pubmed:abstractText
IkappaB kinase beta (IKKbeta), required for NF-kappaB activation, links chronic inflammation with carcinogenesis. We investigated whether IKKbeta is involved in chemically induced liver cancer, a model not involving overt inflammation. Surprisingly, mice lacking IKKbeta only in hepatocytes (Ikkbeta(Deltahep) mice) exhibited a marked increase in hepatocarcinogenesis caused by diethylnitrosamine (DEN). This correlated with enhanced reactive oxygen species (ROS) production, increased JNK activation, and hepatocyte death, giving rise to augmented compensatory proliferation of surviving hepatocytes. Brief oral administration of an antioxidant around the time of DEN exposure blocked prolonged JNK activation and compensatory proliferation and prevented excessive DEN-induced carcinogenesis in Ikkbeta(Deltahep) mice. Decreased hepatocarcinogenesis was also found in mice lacking IKKbeta in both hepatocytes and hematopoietic-derived Kupffer cells. These mice exhibited reduced hepatocyte regeneration and diminished induction of hepatomitogens, which were unaltered in Ikkbeta(Deltahep) mice. IKKbeta, therefore, orchestrates inflammatory crosstalk between hepatocytes and hematopoietic-derived cells that promotes chemical hepatocarcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0092-8674
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
977-90
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15989949-Animals, pubmed-meshheading:15989949-Carcinogens, pubmed-meshheading:15989949-Cell Death, pubmed-meshheading:15989949-Cell Proliferation, pubmed-meshheading:15989949-Cell Transformation, Neoplastic, pubmed-meshheading:15989949-Cytokines, pubmed-meshheading:15989949-Diethylnitrosamine, pubmed-meshheading:15989949-Disease Models, Animal, pubmed-meshheading:15989949-Female, pubmed-meshheading:15989949-Hepatocytes, pubmed-meshheading:15989949-I-kappa B Kinase, pubmed-meshheading:15989949-Inflammation, pubmed-meshheading:15989949-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:15989949-Kupffer Cells, pubmed-meshheading:15989949-Liver Neoplasms, Experimental, pubmed-meshheading:15989949-Liver Regeneration, pubmed-meshheading:15989949-Male, pubmed-meshheading:15989949-Mice, pubmed-meshheading:15989949-Mice, Inbred C57BL, pubmed-meshheading:15989949-Mice, Knockout, pubmed-meshheading:15989949-Mice, Transgenic, pubmed-meshheading:15989949-Oxidative Stress, pubmed-meshheading:15989949-Protein-Serine-Threonine Kinases, pubmed-meshheading:15989949-Reactive Oxygen Species
pubmed:year
2005
pubmed:articleTitle
IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis.
pubmed:affiliation
Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive MC 0723, La Jolla, California 92093, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural