UNASSIGNED: Insulin plays an important role as growth factor and its contribution to @entity5 proliferation is intensely discussed. It acts via the cognate @entity8277 ( @entity8277 ) but can also activate the @entity2856 ( @entity2856 ). Apart from increasing proliferation, insulin might have additional effects in @entity2 . Therefore, we investigated insulin action and effects of @entity8277 @entity1467 ( @entity1467 ) in three (NCI-H292, NCI-H226 and @entity1 ) independent @entity1149 ( @entity1149 ) cell lines. All @entity2 lines studied were found to express @entity8277 , albeit with marked differences in the ratio of the two variants IR-A and IR-B. Insulin activated the classical signaling pathway with @entity8277 autophosphorylation and Akt phosphorylation. Moreover, activation of MAPK (mitogen-activated protein kinases) was observed in H292 cells, accompanied by enhanced proliferation. Lentiviral shRNA IR @entity1467 caused strong decrease in survival of all three lines, indicating that the effects of insulin in @entity2 go beyond enhancing proliferation. Unspecific effects were ruled out by employing further shRNAs and different insulin-responsive cells ( @entity1 pre-adipocytes) for comparison. Caspase assays demonstrated that IR @entity1467 strongly induced apoptosis in these @entity2 cells, providing the physiological basis of the rapid cell loss. In search for the underlying mechanism, we analyzed alterations in the gene expression profile in response to @entity8277 @entity1467 . A strong induction of certain cytokines (e.g. @entity23226 and TNF) became obvious and it turned out that these cytokines trigger apoptosis in the @entity1149 cells tested. This indicates a novel role of @entity8277 in @entity5 cell survival via suppression of pro-apoptotic cytokines.

XXXX cell survival crucially depends on functional insulin receptors.

@entity1 :: ('9606', 'Species') :: ['human', 'NCI-H460'] @entity23226 :: ('50604', 'Gene') :: ['IL20'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small cell lung cancer'] @entity8277 :: ('3643', 'Gene') :: ['insulin receptor', 'IR'] @entity1467 :: ('MESH:D004314', 'Disease') :: ['KD', 'knock-down'] @entity2856 :: ('3480', 'Gene') :: ['IGF1 receptor', 'IGF1R']
@entity1149 :: (MESH:D002289,Disease) :: ['Non-small cell lung cancer']
