Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells

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dc.contributor.authorKwang Kyu Kim-
dc.contributor.authorJung Joon Lee-
dc.contributor.authorY Yang-
dc.contributor.authorK H You-
dc.contributor.authorJ H Lee-
dc.date.accessioned2017-04-19T09:09:57Z-
dc.date.available2017-04-19T09:09:57Z-
dc.date.issued2008-
dc.identifier.issn0143-3334-
dc.identifier.uri10.1093/carcin/bgn031ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/8379-
dc.description.abstractMacrophage 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.publisherOxford Univ Press-
dc.titleMacrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells-
dc.title.alternativeMacrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells-
dc.typeArticle-
dc.citation.titleCarcinogenesis-
dc.citation.number4-
dc.citation.endPage712-
dc.citation.startPage704-
dc.citation.volume29-
dc.contributor.affiliatedAuthorKwang Kyu Kim-
dc.contributor.affiliatedAuthorJung Joon Lee-
dc.contributor.alternativeName김광규-
dc.contributor.alternativeName이정준-
dc.contributor.alternativeName양영-
dc.contributor.alternativeName유관희-
dc.contributor.alternativeName이정형-
dc.identifier.bibliographicCitationCarcinogenesis, vol. 29, no. 4, pp. 704-712-
dc.identifier.doi10.1093/carcin/bgn031-
dc.description.journalClassY-
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