Cited 84 times in
Insulin-Like Growth Factor-Binding Protein 3 Induces Caspase-Dependent Apoptosis through a Death Receptor-Mediated Pathway in MCF-7 Human Breast Cancer Cells
DC Field | Value | Language |
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dc.contributor.author | 김호성 | - |
dc.date.accessioned | 2015-07-14T17:14:53Z | - |
dc.date.available | 2015-07-14T17:14:53Z | - |
dc.date.issued | 2004 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/112501 | - |
dc.description.abstract | Insulin-like growth factor-binding protein (IGFBP)-3 has been shown to potently inhibit cell proliferation in various cell systems. However, the specific mechanisms involved in the antiproliferative action of IGFBP-3 have yet to be elucidated. In the present study, we demonstrate that IGFBP-3 induces apoptosis in an insulin-like growth factor (IGF)-independent manner through the activation of caspases involved in a death receptor-mediated pathway in MCF-7 human breast cancer cells. Induction of IGFBP-3 using an ecdysone-inducible expression system inhibited DNA synthesis in an IGF-IGF receptor axis-independent fashion and resulted in the subsequent induction of apoptosis and an increase in caspase activity. Similar results were obtained when cells were transfected with GGG-IGFBP-3, an IGFBP-3 mutant unable to bind IGFs, corroborating the IGF-independent action of IGFBP-3. Additional caspase activity studies and immunoblot analyses using specific caspase substrates and/or caspase inhibitors revealed that the growth-inhibitory effect of IGFBP-3 results mainly from its induction of apoptosis (in particular, activation of caspase-8 and -7). Analyses of caspase-9 activity and release of cytochrome c into the cytosol confirmed that the mitochondria-mediated pathway is not involved. Taken together, these results show that IGFBP-3 expression leads to the induction of apoptosis through the activation of caspases involved in a death receptor-mediated pathway and that IGFBP-3 functions as a negative regulator of breast cancer cell growth, independent of the IGF-IGF receptor axis. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 2229~2237 | - |
dc.relation.isPartOf | CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Insulin-Like Growth Factor-Binding Protein 3 Induces Caspase-Dependent Apoptosis through a Death Receptor-Mediated Pathway in MCF-7 Human Breast Cancer Cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pediatrics (소아과학) | - |
dc.contributor.googleauthor | Ho-Seong Kim | - |
dc.contributor.googleauthor | Angela R. Ingermann | - |
dc.contributor.googleauthor | Youngman Oh | - |
dc.contributor.googleauthor | Gillian E. Walker | - |
dc.contributor.googleauthor | Stephen M. Twigg | - |
dc.contributor.googleauthor | Junko Tsubaki | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-03-1675 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.relation.journalcode | J00452 | - |
dc.identifier.eissn | 1538-7445 | - |
dc.contributor.alternativeName | Kim, Ho Seong | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 64 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 2229 | - |
dc.citation.endPage | 2237 | - |
dc.identifier.bibliographicCitation | CANCER RESEARCH, Vol.64(6) : 2229-2237, 2004 | - |
dc.identifier.rimsid | 56220 | - |
dc.type.rims | ART | - |
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