Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 박혜영 | - |
dc.date.accessioned | 2018-12-07T16:30:51Z | - |
dc.date.available | 2018-12-07T16:30:51Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1226-3613 | - |
dc.identifier.other | OAK-20485 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/247452 | - |
dc.description.abstract | The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells. Treatment of 4T1 cells with CXCL10 increased the expression of P65, a subunit of the NF-κB pathway, via activation of the NF-κB transcriptional activity. Ectopic overexpression of P65 increased CXCL10 secretion and blunted JN-2-induced suppression of CXCL10 secretion, whereas overexpression of IκBa suppressed CXCL10 secretion. These results indicate that the CXCL10/CXCR3 axis creates a positive feedback loop through the canonical NF-κB signaling pathway in 4T1 cells. In addition, treatment of osteoblasts with conditioned medium from JN-2-treated 4T1 cells inhibited the expression of RANKL, a crucial cytokine for osteoclast differentiation, which resulted in an inhibitory effect on osteoclast differentiation in the co-culture system of bone marrowderived macrophages and osteoblasts. Direct intrafemoral injection of 4T1 cells induced severe bone destruction; however, this effect was suppressed by the CXCR3 antagonist via downregulation of P65 expression in an animal model. Collectively, these results suggest that the CXCL10/CXCR3-mediated NF-κB signaling pathway plays a role in the control of autonomous regulation of CXCL10 and malignant tumor properties in breast cancer 4T1 cells. © 2017 KSBMB. All rights reserved. | - |
dc.description.sponsorship | Ministry of Science, ICT and Future Planning | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.title | NF-κB signaling regulates cell-autonomous regulation of CXCL10 in breast cancer 4T1 cells | - |
dc.type | Article | - |
dc.relation.issue | 2 | - |
dc.relation.volume | 49 | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.index | KCI | - |
dc.relation.journaltitle | Experimental and Molecular Medicine | - |
dc.identifier.doi | 10.1038/emm.2016.148 | - |
dc.identifier.wosid | WOS:000397015000006 | - |
dc.identifier.scopusid | 2-s2.0-85025083944 | - |
dc.author.google | Jin W.J. | - |
dc.author.google | Kim B. | - |
dc.author.google | Kim D. | - |
dc.author.google | Choo H.-Y.P. | - |
dc.author.google | Kim H.-H. | - |
dc.author.google | Ha H. | - |
dc.author.google | Lee Z.H. | - |
dc.contributor.scopusid | 박혜영(34972649500;57200273796) | - |
dc.date.modifydate | 20230411110509 | - |