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rdf:type |
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lifeskim:mentions |
umls-concept:C0007600,
umls-concept:C0040690,
umls-concept:C0153690,
umls-concept:C0205314,
umls-concept:C0332307,
umls-concept:C0597357,
umls-concept:C0679622,
umls-concept:C1171350,
umls-concept:C1269955,
umls-concept:C1512505,
umls-concept:C1515655,
umls-concept:C1533691,
umls-concept:C1956526,
umls-concept:C2699153
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pubmed:issue |
1
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pubmed:dateCreated |
2007-4-10
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pubmed:abstractText |
Transforming growth factor (TGF)-beta signaling has been shown to promote tumor growth and metastasis in advanced cancer. Use of inhibitors of TGF-beta signaling may thus be a novel strategy for treatment of patients with such cancers. In this study, we investigated the effects of a novel TGF-beta type I receptor (TbetaR-I) kinase inhibitor, Ki26894, on bone metastasis of a highly bone-metastatic variant of human breast cancer MDA-MB-231 cells, termed MDA-MB-231-5a-D (MDA-231-D). Ki26894 blocked TGF-beta signaling in MDA-231-D cells, as detected by suppression of phosphorylation of Smad2 and inhibition of TGF-beta-responsive reporter activity. Moreover, Ki26894 decreased the motility and the invasion of MDA-231-D cells induced by TGF-beta in vitro. Ki26894 also suppressed transcription of plasminogen activator inhibitor-1 (PAI-1), parathyroid hormone-related protein (PTHrP), and interleukin-11 (IL-11) mRNA of MDA-231-D cells, which were stimulated by TGF-beta. X-ray radiography revealed that systemic Ki26894 treatment initiated 1 day before the inoculation of MDA-231-D cells into the left ventricle of BALB/cnu/nu female mice resulted in decreased bone metastasis of breast cancer cells. Moreover, Ki26894 prolonged the survival of mice inoculated with MDA-231-D cells compared to vehicle-treated mice. These findings suggest that TbetaR-I kinase inhibitors such as Ki26894 may be useful for blocking the progression of advanced cancers.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1347-9032
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pubmed:author |
pubmed-author:EhataShogoS,
pubmed-author:FujimeMakotoM,
pubmed-author:FukunagaErinaE,
pubmed-author:GotoKouichiroK,
pubmed-author:HanyuAkiA,
pubmed-author:ImamuraTakeshiT,
pubmed-author:IshikawaYuichiY,
pubmed-author:KatsunoYokoY,
pubmed-author:MiyazonoKoheiK,
pubmed-author:NomuraKimieK,
pubmed-author:OgataEtsuroE,
pubmed-author:ShimizuKiyoshiK,
pubmed-author:ShimizuToshiyukiT,
pubmed-author:YokooHiroshiH
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pubmed:issnType |
Print
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pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
127-33
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17129361-Activin Receptors, Type I,
pubmed-meshheading:17129361-Animals,
pubmed-meshheading:17129361-Antineoplastic Agents,
pubmed-meshheading:17129361-Bone Neoplasms,
pubmed-meshheading:17129361-Female,
pubmed-meshheading:17129361-Humans,
pubmed-meshheading:17129361-Immunoblotting,
pubmed-meshheading:17129361-Mammary Neoplasms, Experimental,
pubmed-meshheading:17129361-Mice,
pubmed-meshheading:17129361-Neoplasm Invasiveness,
pubmed-meshheading:17129361-Neoplasm Metastasis,
pubmed-meshheading:17129361-Protein Kinase Inhibitors,
pubmed-meshheading:17129361-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17129361-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:17129361-Reverse Transcriptase Polymerase Chain Reaction
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pubmed:year |
2007
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pubmed:articleTitle |
Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line.
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pubmed:affiliation |
Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Koto-ku, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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