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| 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
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| 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
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| 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.
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| Contributor(s) |
Yu J, Zhang L |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jul 13, 2007 |
| Last update date |
Jan 18, 2013 |
| Contact name |
yu jian |
| E-mail(s) |
yujian@capitalbio.com
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| Phone |
(86)-10-80726868
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| Fax |
(86)-10-62773059
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| Organization name |
Tsinghua University
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| Department |
Medical Systems Biology Research Center
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| Street address |
Qinghuayuan
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| City |
Beijing |
| State/province |
Beijing |
| ZIP/Postal code |
100084 |
| Country |
China |
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| Platforms (1) |
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| Samples (5)
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| GSM210120 |
Smad4-independent genes in BxPC-3 cells |
| GSM210121 |
Smad2-independent genes in BxPC-3 cells |
| GSM210122 |
Smad2-dependent genes in BxPC-3 cells |
| GSM210123 |
Smad3-independent genes in BxPC-3 cells |
| GSM210124 |
Smad3-dependent genes in BxPC-3 cells |
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| Relations |
| BioProject |
PRJNA101547 |
| 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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