Gene Set: BROCKE_APOPTOSIS_REVERSED_BY_IL6

Standard name BROCKE_APOPTOSIS_REVERSED_BY_IL6
Systematic name M8244
Brief description Genes changed in INA-6 cells (multiple myeloma, MM) by re-addition of IL6 [GeneID=3569] after its initial withdrawal for 12h.
Full description or abstract Interleukin 6 (IL-6) is a growth and survival factor for multiple myeloma cells. As we report here, the IL-6-dependent human myeloma cell line INA-6 responds with a remarkably rapid and complete apoptosis to cytokine withdrawal. Among the antiapoptotic members of the B-cell lymphoma-2 (Bcl-2) family of apoptosis regulators, only myeloid cell factor-1 (Mcl-1) was slightly induced by IL-6. Overexpression studies demonstrated, however, that IL-6 does not exert its survival effect primarily through this pathway. The IL-6 signal transduction pathways required for survival and the target genes controlled by them were analyzed by using mutated receptor chimeras. The activation of signal transducer and activator of transcription 3 (Stat3) turned out to be obligatory for the survival of INA-6 cells. The same held true for survival and growth of XG-1 myeloma cells. Gene expression profiling of INA-6 cells by using oligonucleotide microarrays revealed many novel IL-6 target genes, among them several genes coding for transcriptional regulators involved in B-lymphocyte differentiation as well as for growth factors and receptors potentially implicated in autocrine or paracrine growth control. Regulation of most IL-6 target genes required the activation of Stat3, underscoring its central role for IL-6 signal transduction. Taken together, our data provide evidence for the existence of an as yet unknown Stat3-dependent survival pathway in myeloma cells.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 12969979   Authors: Brocke-Heidrich K,Kretzschmar AK,Pfeifer G,Henze C,Löffler D,Koczan D,Thiesen HJ,Burger R,Gramatzki M,Horn F
Exact source Table 1S
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Organism Homo sapiens
Contributed by Kate Stafford (MSigDB Team)
Source platform AFFY_HG_U95
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Version history 3.0: Renamed from BROCKE_IL6

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