Cited 65 times in
Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1-mediated transcriptional events
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이옥희 | - |
dc.date.accessioned | 2014-12-20T17:22:57Z | - |
dc.date.available | 2014-12-20T17:22:57Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/94496 | - |
dc.description.abstract | Most antiangiogenic therapies currently being evaluated in clinical trials target the vascular endothelial growth factor pathway; however, the tumor vasculature can acquire resistance to vascular endothelial growth factor-targeted therapy by shifting to other angiogenesis mechanisms. Insulin-like growth factor binding protein-3 (IGFBP-3) has been reported to suppress tumor growth and angiogenesis by both IGF-dependent and IGF-independent mechanisms; however, understanding of its IGF-independent mechanisms is limited. We observed that IGFBP-3 blocked tumor angiogenesis and growth in non-small cell lung cancer and head and neck squamous cell carcinoma. Conditioned media from an IGFBP-3-treated non-small cell lung cancer cell line displayed a significantly decreased capacity to induce HUVEC proliferation and aortic sprouting. In cancer cells, IGFBP-3 directly interacted with Erk1/2, leading to inactivation of Erk1/2 and Elk-1, and suppressed transcription of early growth response protein 1 and its target genes, basic fibroblast growth factor and platelet-derived growth factor. These data suggest that IGF-independent Erk1/2 inactivation and decreased IGFBP-3-induced Egr-1 expression block the autocrine and paracrine loops of angiogenic factors in vascular endothelial and cancer cells. Together, these findings provide a molecular framework of IGFBP-3's IGF-independent antiangiogenic antitumor activities. Future studies are needed for development of IGFBP-3 as a new line of antiangiogengic cancer drug. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 2622~2631 | - |
dc.relation.isPartOf | BLOOD | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Angiogenesis Inhibitors/metabolism | - |
dc.subject.MESH | Angiogenesis Inhibitors/pharmacology* | - |
dc.subject.MESH | Angiogenesis Inhibitors/therapeutic use | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Carcinoma/blood supply | - |
dc.subject.MESH | Carcinoma/drug therapy* | - |
dc.subject.MESH | Carcinoma/pathology | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung/blood supply | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung/drug therapy* | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung/pathology | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cells, Cultured/cytology | - |
dc.subject.MESH | Cells, Cultured/drug effects | - |
dc.subject.MESH | Chick Embryo | - |
dc.subject.MESH | Early Growth Response Protein 1/genetics* | - |
dc.subject.MESH | Early Growth Response Protein 1/metabolism | - |
dc.subject.MESH | Endothelial Cells/cytology | - |
dc.subject.MESH | Endothelial Cells/drug effects | - |
dc.subject.MESH | Enzyme Activation/drug effects | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Gene Expression Regulation, Neoplastic/drug effects* | - |
dc.subject.MESH | Head and Neck Neoplasms/blood supply | - |
dc.subject.MESH | Head and Neck Neoplasms/drug therapy* | - |
dc.subject.MESH | Head and Neck Neoplasms/pathology | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Insulin-Like Growth Factor Binding Protein 3/metabolism | - |
dc.subject.MESH | Insulin-Like Growth Factor Binding Protein 3/pharmacology* | - |
dc.subject.MESH | Insulin-Like Growth Factor Binding Protein 3/therapeutic use | - |
dc.subject.MESH | Lung Neoplasms/blood supply | - |
dc.subject.MESH | Lung Neoplasms/drug therapy* | - |
dc.subject.MESH | Lung Neoplasms/pathology | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | Mitogen-Activated Protein Kinase 1/antagonists & inhibitors* | - |
dc.subject.MESH | Mitogen-Activated Protein Kinase 1/metabolism | - |
dc.subject.MESH | Mitogen-Activated Protein Kinase 3/antagonists & inhibitors* | - |
dc.subject.MESH | Mitogen-Activated Protein Kinase 3/metabolism | - |
dc.subject.MESH | Neoplasm Proteins/antagonists & inhibitors | - |
dc.subject.MESH | Neoplasm Proteins/biosynthesis | - |
dc.subject.MESH | Neoplasm Proteins/genetics | - |
dc.subject.MESH | Neoplasm Proteins/metabolism | - |
dc.subject.MESH | Neovascularization, Pathologic/drug therapy* | - |
dc.subject.MESH | Promoter Regions, Genetic/drug effects* | - |
dc.subject.MESH | Recombinant Fusion Proteins/pharmacology | - |
dc.subject.MESH | Recombinant Fusion Proteins/therapeutic use | - |
dc.subject.MESH | Specific Pathogen-Free Organisms | - |
dc.subject.MESH | Transcription, Genetic/drug effects* | - |
dc.subject.MESH | Xenograft Model Antitumor Assays | - |
dc.subject.MESH | ets-Domain Protein Elk-1/metabolism* | - |
dc.title | Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1-mediated transcriptional events | - |
dc.type | Article | - |
dc.contributor.college | Researcher Institutes (부설 연구소) | - |
dc.contributor.department | Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) | - |
dc.contributor.googleauthor | Jai-Hyun Kim | - |
dc.contributor.googleauthor | Dong Soon Choi | - |
dc.contributor.googleauthor | Ok-Hee Lee | - |
dc.contributor.googleauthor | Seung-Hyun Oh | - |
dc.contributor.googleauthor | Scott M. Lippman | - |
dc.contributor.googleauthor | Ho-Young Lee | - |
dc.identifier.doi | 10.1182/blood-2010-08-299784 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02970 | - |
dc.relation.journalcode | J00341 | - |
dc.identifier.eissn | 1528-0020 | - |
dc.identifier.pmid | 21551235 | - |
dc.contributor.alternativeName | Lee, Ok Hee | - |
dc.contributor.affiliatedAuthor | Lee, Ok Hee | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 118 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 2622 | - |
dc.citation.endPage | 2631 | - |
dc.identifier.bibliographicCitation | BLOOD, Vol.118(9) : 2622-2631, 2011 | - |
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