Linked Life Data

10766192

Source:http://linkedlifedata.com/resource/pubmed/id/10766192

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2000-5-4
pubmed:abstractText
Resistance of cancer cells against apoptosis induced by death factors contributes to the limited efficiency of immune- and drug-induced destruction of tumors. We report here that insulin and insulin-like growth factor-I (IGF-I) fully protect HT29-D4 colon carcinoma cells from IFN-gamma/tumor necrosis factor-alpha (TNF) induced apoptosis. Survival signaling initiated by IGF-I was not dependent on the canonical survival pathway involving phosphatidylinositol 3'-kinase. In addition, neither pp70(S6K) nor protein kinase C conveyed IGF-I antiapoptotic function. Inhibition of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) with the MAPK/ERK kinase inhibitor PD098059 and MAPK/p38 with the specific inhibitor SB203580 partially reversed, in a nonadditive manner, the IGF-I survival effect. Inhibition of nuclear factor kappaB (NF-kappaB) activity by preventing degradation of the inhibitor of NF-kappaB (IkappaB-alpha) with BAY 11-7082 also blocked in part the IGF-I antiapoptotic effect. However, the complete reversal of the IGF-I effect was obtained only when NF-kappaB and either MAPK/ERK or MAPK/p38 were inhibited together. Because these pathways are also those used by TNF to signal inflammation and survival, these data point to a cross talk between IGF-I- and TNF-induced signaling. We further report that TNF-induced IL-8 production was indeed strongly enhanced upon IGF-I addition, and this effect was totally abrogated by both MAPK and NF-kappaB inhibitors. The IGF-I antiapoptotic function was stimulus-dependent because Fas- and IFN/Fas-induced apoptosis was not efficiently inhibited by IGF-I. This was correlated with the weak ability of Fas ligation to enhance IL-8 production in the presence or absence of IGF-I. These findings indicate that the antiapoptotic function of IGF-I in HT29-D4 cells is based on the enhancement of the survival pathways initiated by TNF, but not Fas, and mediated by MAPK/p38, MAPK/ERK, and NF-kappaB, which act in concert to suppress the proapoptotic signals. In agreement with this model, we show that it was possible to render HT29-D4 cells resistant to Fas-induced apoptosis provided that IGF-I and TNF receptors were activated simultaneously.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2007-17
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10766192-Adenocarcinoma, pubmed-meshheading:10766192-Antibodies, Monoclonal, pubmed-meshheading:10766192-Antigens, CD, pubmed-meshheading:10766192-Apoptosis, pubmed-meshheading:10766192-Colonic Neoplasms, pubmed-meshheading:10766192-DNA Fragmentation, pubmed-meshheading:10766192-Humans, pubmed-meshheading:10766192-Insulin-Like Growth Factor I, pubmed-meshheading:10766192-Interferon-gamma, pubmed-meshheading:10766192-Interleukin-8, pubmed-meshheading:10766192-Receptors, Tumor Necrosis Factor, pubmed-meshheading:10766192-Receptors, Tumor Necrosis Factor, Type I, pubmed-meshheading:10766192-Receptors, Tumor Necrosis Factor, Type II, pubmed-meshheading:10766192-Recombinant Proteins, pubmed-meshheading:10766192-Tumor Cells, Cultured, pubmed-meshheading:10766192-Tumor Necrosis Factor-alpha
pubmed:year
2000
pubmed:articleTitle
Insulin-like growth factor-I protects colon cancer cells from death factor-induced apoptosis by potentiating tumor necrosis factor alpha-induced mitogen-activated protein kinase and nuclear factor kappaB signaling pathways.
pubmed:affiliation
Unité 6032, Interactions entre Systèmes Protéiques et Différenciation dans la Cellule Tumorale, Centre National de la Recherche Scientifique, Faculté de Médecine, Marseille, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't