Human Gene Set: JAZAG_TGFB1_SIGNALING_VIA_SMAD4_DN


Standard name JAZAG_TGFB1_SIGNALING_VIA_SMAD4_DN
Systematic name M18705
Brief description Genes down-regulated in PANC-1-S4KD cells (pancreatic cancer; SMAD4 [GeneID=4089] knocked down by RNAi) after stimulation by TGF1B [GeneID=7040] for 2 h.
Full description or abstract The transforming growth factor-beta (TGF-beta)-Smad signaling pathway inhibits the growth of human epithelial cells and plays a role in tumor suppression. The Smad4 gene is mutated or deleted in 50% of pancreatic cancers. In this study, we succeeded in establishing Smad4 knockdown (S4KD) pancreatic cancer cell lines using the stable RNA interference (RNAi) method. Smad4 protein expression was reduced dramatically and TGF-beta-Smad signaling was markedly inhibited in the S4KD cell lines. The S4KD and control cells were stimulated with TGF-beta and analysed using a cDNA microarray that contained 3756 genes, in order to screen for target molecules downstream of TGF-beta. The microarray analysis revealed that 187 S4KD genes and 155 genes in the control cells were regulated immediately upon TGF-beta stimulation. Quantitative RT-PCR analysis on several of these genes produced results that corroborated the outcome of the microarray analysis. Most of the genes in the S4KD and control cells identified by the array differed, which suggests signaling pathways that differ according to Smad4 status. Of the identified genes, 246 have not been reported previously as genes that lie downstream of TGF-beta. Genes that are involved in cell proliferation, adhesion, and motility were found to be regulated differentially with respect to S4KD and control cells. Cell migration induced by TGF-beta was inhibited in the S4KD cells, which might be associated with a different regulation of integrin beta7. The knock down of a specific gene using stable RNAi appears to be a promising tool for analysing endogenous gene function.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15592526   Authors: Jazag A,Ijichi H,Kanai F,Imamura T,Guleng B,Ohta M,Imamura J,Tanaka Y,Tateishi K,Ikenoue T,Kawakami T,Arakawa Y,Miyagishi M,Taira K,Kawabe T,Omata M
Exact source Table 3bS: Fold change <= 0.5
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Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.0: First introduced

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