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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2004-2-5
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pubmed:abstractText |
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, the Smad4-null pancreatic cancer cell line BxPC-3 was transfected with either the Smad4 expression vector or the empty vector and incubated in the presence or absence of TGF-beta. The cells were analysed using a cDNA microarray, which included 2280 named genes to screen for target genes regulated by TGF-beta in either a Smad4-dependent or -independent manner. The microarray and subsequent quantitative RT-PCR analysis demonstrated that the Smad4-independent and -dependent signaling pathways driven by TGF-beta upregulated only one of the 2280 genes, respectively, suggesting that Smad4-independent signaling downstream of TGF-beta might be as widespread as Smad4-dependent signaling. In this study, we demonstrated that the cyclin-dependent kinase inhibitor p21/WAF1, which has been considered the major effector of the Smad-dependent growth inhibitory signal of TGF-beta, is upregulated in a Smad4-independent manner. The upregulation occurs through Smad2/3-dependent transcriptional activation of the p21/WAF1 promoter region. These results suggest a novel mechanism of gene regulation, that is, a novel signal mediator other than Smad4.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/DCP1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endoribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0950-9232
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pubmed:author |
pubmed-author:ArakawaYoshihiroY,
pubmed-author:IjichiHideakiH,
pubmed-author:IkenoueTsuneoT,
pubmed-author:KanaiFumihikoF,
pubmed-author:KawabeTakaoT,
pubmed-author:KawakamiTakayukiT,
pubmed-author:MiyazonoKoheiK,
pubmed-author:OmataMasaoM,
pubmed-author:OtsukaMotoyukiM,
pubmed-author:SekiNaohikoN,
pubmed-author:ShimizuKiyoshiK,
pubmed-author:TateishiKeisukeK
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1043-51
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pubmed:dateRevised |
2009-11-11
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pubmed:meshHeading |
pubmed-meshheading:14762439-Active Transport, Cell Nucleus,
pubmed-meshheading:14762439-Cell Division,
pubmed-meshheading:14762439-Cell Line, Tumor,
pubmed-meshheading:14762439-Cell Nucleus,
pubmed-meshheading:14762439-Cells, Cultured,
pubmed-meshheading:14762439-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:14762439-Cyclins,
pubmed-meshheading:14762439-DNA, Complementary,
pubmed-meshheading:14762439-DNA-Binding Proteins,
pubmed-meshheading:14762439-Endoribonucleases,
pubmed-meshheading:14762439-Enzyme Induction,
pubmed-meshheading:14762439-Gene Deletion,
pubmed-meshheading:14762439-Gene Expression Regulation,
pubmed-meshheading:14762439-Genes, Tumor Suppressor,
pubmed-meshheading:14762439-Humans,
pubmed-meshheading:14762439-Keratinocytes,
pubmed-meshheading:14762439-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:14762439-Pancreatic Neoplasms,
pubmed-meshheading:14762439-Promoter Regions, Genetic,
pubmed-meshheading:14762439-RNA, Messenger,
pubmed-meshheading:14762439-Signal Transduction,
pubmed-meshheading:14762439-Smad2 Protein,
pubmed-meshheading:14762439-Smad3 Protein,
pubmed-meshheading:14762439-Trans-Activators,
pubmed-meshheading:14762439-Transcriptional Activation,
pubmed-meshheading:14762439-Transforming Growth Factor beta
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pubmed:year |
2004
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pubmed:articleTitle |
Smad4-independent regulation of p21/WAF1 by transforming growth factor-beta.
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pubmed:affiliation |
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. ijichi-2im@h.u-tokyo.ac.jp
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pubmed:publicationType |
Journal Article
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