DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kwang Kyu Kim | - |
dc.contributor.author | Jung Joon Lee | - |
dc.contributor.author | Y Yang | - |
dc.contributor.author | K H You | - |
dc.contributor.author | J H Lee | - |
dc.date.accessioned | 2017-04-19T09:09:57Z | - |
dc.date.available | 2017-04-19T09:09:57Z | - |
dc.date.issued | 2008 | - |
dc.identifier.issn | 0143-3334 | - |
dc.identifier.uri | 10.1093/carcin/bgn031 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/8379 | - |
dc.description.abstract | Macrophage inhibitory cytokine-1 (MIC-1) is a member of the transforming growth factor-β superfamily, which is overexpressed in a variety of human cancers, including breast and gastric cancer. The function of MIC-1 in cancer remains controversial and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of ErbB2 in SK-BR-3 breast and SNU-216 gastric cancer cells. MIC-1 induced a significant phosphorylation of Akt and ERK-1/2, and also effected an increase in the levels of tyrosine phosphorylation of ErbB1, ErbB2 and ErbB3 in SK-BR-3 and SNU-216 cells. The treatment of these cells with AG825 and AG1478, inhibitors specific for ErbB2 tyrosine kinase, resulted in the complete abolition of MIC-1-induced Akt and ERK-1/2 phosphorylation. Furthermore, the small-interfering RNA-mediated downregulation of ErbB2 significantly reduced not only the phosphorylation of Akt and ERK-1/2 but also the invasiveness of the cells induced by MIC-1. Our results show that ErbB2 activation performs a crucial function in MIC-1-induced signaling pathways. Further investigations revealed that MIC-1 induced the expression of the hypoxia inducible factor-1α protein and the expression of its target genes, including vascular endothelial growth factor, via the activation of the mammalian target of rapamycin (mTOR) signaling pathway. Stimulation of SK-BR-3 with MIC-1 profoundly induces the phosphorylation of mTOR and its downstream substrates, including p70S6K and 4E-BP1. Collectively, these results show that MIC-1 may participate in the malignant progression of certain human cancer cells that overexpress ErbB2 through the transactivation of ErbB2 tyrosine kinase. | - |
dc.publisher | Oxford Univ Press | - |
dc.title | Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells | - |
dc.title.alternative | Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells | - |
dc.type | Article | - |
dc.citation.title | Carcinogenesis | - |
dc.citation.number | 4 | - |
dc.citation.endPage | 712 | - |
dc.citation.startPage | 704 | - |
dc.citation.volume | 29 | - |
dc.contributor.affiliatedAuthor | Kwang Kyu Kim | - |
dc.contributor.affiliatedAuthor | Jung Joon Lee | - |
dc.contributor.alternativeName | 김광규 | - |
dc.contributor.alternativeName | 이정준 | - |
dc.contributor.alternativeName | 양영 | - |
dc.contributor.alternativeName | 유관희 | - |
dc.contributor.alternativeName | 이정형 | - |
dc.identifier.bibliographicCitation | Carcinogenesis, vol. 29, no. 4, pp. 704-712 | - |
dc.identifier.doi | 10.1093/carcin/bgn031 | - |
dc.description.journalClass | Y | - |
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