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Series GSE8464 Query DataSets for GSE8464
Status Public on Sep 01, 2007
Title Invasion control by a positive feedback loop mechanism Smad4-null cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary New findings demonstrate that transcriptional factors alternative to Smad4 can bind to Smad2/3 and mediate different transcriptional effects. In this study, we detected constitutively phosphorylation of Smad2/3 in Smad4-null pancreatic cancer cell line BxPC-3. Both pan-specific TGF-β-neutralizing antibody and specific TGF-β type I receptor (TβR-I) inhibitor, SB-431542, can decrease steady-state p-Smad2/3 levels. Moreover, exogenous TGF-β strongly stimulated translocation of phosphorylated Smad2/3 (p-Smad2/3) into the nucleus. Therefore, we identified TGF-β-responsive genes using genome-wide oligonucleotide microarrays and confirmed their dependency on Smad2/3 by the combination of RNA interference (RNAi) and microarray assay. The major finding from our microarray analysis was that of the 262 target genes seen to be regulated via TGF-β induction, 87 were differentially transcriptionally controlled by Smad2/3 signaling and 175 were Smad2/3-independent. Our results showed that integrin β6 was transcriptionally up-regulated via TGF-β induction in a Smad3-dependent manner, which was validated by real-time RT-PCR and western blot. We also provide evidence that αVβ6 integrin can activate TGF-β-Smad2/3 signaling. Thus, we for the first time suggest the positive feedback loop compose of TGF-β-Smad3 signaling and integrin β6. Functional analysis revealed that exogenous TGF-β can amplify the invasive property of Smad4-deficient pancreatic cancer cells; however, TGF-β-neutralizing antibody, specific TβR-I inhibitor, and anti-αVβ6 integrin antibody can reduce it. Therefore, integrin β6 mediated the invasion of BxPC-3 cells induced by TGF-β signaling.
Keywords: cell type comparison
Overall design Large-scale microarray analysis was employed for comparison between the responses of wild-type BxPC-3 cell line and each knockdown cell line, with and without TGF-β induction, to identify target genes.
Contributor(s) Yu J, Zhang L
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Submission date Jul 13, 2007
Last update date Jan 18, 2013
Contact name yu jian
Phone (86)-10-80726868
Fax (86)-10-62773059
Organization name Tsinghua University
Department Medical Systems Biology Research Center
Street address Qinghuayuan
City Beijing
State/province Beijing
ZIP/Postal code 100084
Country China
Platforms (1)
GPL4525 Human 22K long oligo array
Samples (5)
GSM210120 Smad4-independent genes in BxPC-3 cells
GSM210121 Smad2-independent genes in BxPC-3 cells
GSM210122 Smad2-dependent genes in BxPC-3 cells
BioProject PRJNA101547

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE8464_RAW.tar 14.0 Mb (http)(custom) TAR (of LSR)
Processed data included within Sample table

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