| http://purl.uniprot.org/citations/12140283 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12140283 | http://www.w3.org/2000/01/rdf-schema#comment | "Overexpression of the small leucine-rich proteoglycan biglycan (BGN) in fibrosis and desmoplasia results from enhanced activity of transforming growth factor-beta (TGF-beta). In pancreatic adenocarcinoma, the tumor cells themselves may contribute to BGN synthesis in vivo, since 8 of 18 different pancreatic carcinoma cell lines constitutively expressed BGN mRNA, as shown by reverse transcription-PCR analysis. In PANC-1 cells, TGF-beta1 dramatically stimulated BGN mRNA accumulation through a BGN transcription-independent, cycloheximide-sensitive mechanism and strongly increased the synthesis and release of the proteoglycan form of BGN. The ability of TGF-beta1 to induce BGN mRNA was critically dependent on Smad signaling, since 1) the up-regulation of BGN mRNA was preceded by a marked increase in Smad2 phosphorylation in TGF-beta1-treated PANC-1 cells, 2) TGF-beta1 was unable to induce BGN mRNA in pancreatic carcinoma cell lines that carry homozygous deletions of the Smad4/DPC4 gene, 3) inhibition of the Smad pathway in PANC-1 cells by transfection with a dominant negative Smad4/DPC4 mutant significantly reduced TGF-beta1-induced BGN mRNA expression, 4) stable reintroduction of wild type Smad4/DPC4 into Smad4-null CFPAC-1 cells restored the TGF-beta1 effect, and 5) overexpression of Smad2 and Smad3 in PANC-1 cells augmented TGF-beta1 induction of BGN mRNA, whereas forced expression of Smad7, an inhibitory Smad, effectively blocked it. These results clearly show that a functional Smad pathway is crucial for TGF-beta regulation of BGN mRNA expression. Since BGN has been shown to inhibit growth of pancreatic cancer cells, the Smad4/DPC4 mediation of the TGF-beta effect may represent a novel tumor suppressor function for Smad4/DPC4: antiproliferation via expression of autoinhibitory BGN."xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m203709200"xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/author | "Kalthoff H."xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/author | "Chen W.B."xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/author | "Fischer J.W."xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/author | "Ungefroren H."xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/author | "Lenschow W."xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/author | "Tiede K."xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/pages | "36118-36128"xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/title | "Smad4/DPC4-dependent regulation of biglycan gene expression by transforming growth factor-beta in pancreatic tumor cells."xsd:string |
| http://purl.uniprot.org/citations/12140283 | http://purl.uniprot.org/core/volume | "277"xsd:string |
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