Opposite functions of HIF-alpha isoforms in VEGF induction by TGF-beta 1 under non-hypoxic conditions
DC Field | Value | Language |
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dc.contributor.author | Chae, K. S. | - |
dc.contributor.author | Kang, M. J. | - |
dc.contributor.author | Lee, J. H. | - |
dc.contributor.author | Ryu, B. K. | - |
dc.contributor.author | Lee, M. G. | - |
dc.contributor.author | Her, N. G. | - |
dc.contributor.author | Ha, T. K. | - |
dc.contributor.author | Han, J. | - |
dc.contributor.author | Kim, Y. K. | - |
dc.contributor.author | Chi, S. G. | - |
dc.date.accessioned | 2021-09-07T14:46:40Z | - |
dc.date.available | 2021-09-07T14:46:40Z | - |
dc.date.created | 2021-06-14 | - |
dc.date.issued | 2011-03 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/113014 | - |
dc.description.abstract | Transforming growth factor (TGF)-beta 1 has biphasic functions in prostate tumorigenesis, having a growth-inhibitory effect in the early stages, but in the late stages promoting tumor angiogenesis and metastasis. We demonstrate here that tumor-producing TGF-beta 1 induces vascular endothelial growth factor (VEGF) in prostate cancer cells, and hypoxia-inducible factor (HIF)-1 alpha and HIF-2 alpha has opposite functions in TGF-beta 1 regulation of VEGF expression under non-hypoxic conditions. The promoter response of VEGF to TGF-beta 1 was upregulated by the transfection of HIF-2 alpha or siHIF-1 alpha but downregulated by HIF-1 alpha and siHIF-2 alpha. Both HIF-1 alpha and HIF-2 alpha were induced by TGF-beta 1 at mRNA and protein levels, however, their nuclear translocation was differentially regulated by TGF-beta 1, suggesting its association with their opposite effects. VEGF induction by TGF-beta 1 occurred in a Smad3-dependent manner, and the Smad-binding element 2 (SBE2, -992 to -986) and hypoxia response element (-975 to -968) in the VEGF promoter were required for the promoter response to TGF-beta 1. Smad3 cooperated with HIF-2 alpha in TGF-beta 1 activation of VEGF transcription and Smad3 binding to the SBE2 site was greatly impaired by knockdown of HIF-2 alpha expression. Moreover, the VEGF promoter response to TGF-beta 1 was synergistically elevated by co-transfection of Smad3 and HIF-2 alpha but attenuated by HIF-1 alpha in a dose-dependent manner. Additionally, TGF-beta 1 was found to increase the stability of VEGF transcript by facilitating the cytoplasmic translocation of a RNA-stabilizing factor HuR. Collectively, our data show that tumor-producing TGF-beta 1 induces VEGF at the both transcription and post-transcriptional levels through multiple routes including Smad3, HIF-2 alpha and HuR. This study thus suggests that autocrine TGF-beta 1 production may contribute to tumor angiogenesis via HIF-2 alpha signaling under non-hypoxic conditions, providing a selective growth advantage for prostate tumor cells. Oncogene (2011) 30, 1213-1228; doi:10.1038/onc.2010.498; published online 8 November 2010 | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject | HUMAN PROSTATE-CANCER | - |
dc.subject | HYPOXIA-INDUCIBLE FACTOR-1 | - |
dc.subject | MESSENGER-RNA STABILITY | - |
dc.subject | FACTOR GENE-EXPRESSION | - |
dc.subject | RENAL-CELL CARCINOMA | - |
dc.subject | FACTOR-BETA | - |
dc.subject | CYCLOOXYGENASE-2 EXPRESSION | - |
dc.subject | HIF-2-ALPHA EXPRESSION | - |
dc.subject | FACTOR (HIF)-1-ALPHA | - |
dc.title | Opposite functions of HIF-alpha isoforms in VEGF induction by TGF-beta 1 under non-hypoxic conditions | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, M. G. | - |
dc.contributor.affiliatedAuthor | Kim, Y. K. | - |
dc.contributor.affiliatedAuthor | Chi, S. G. | - |
dc.identifier.doi | 10.1038/onc.2010.498 | - |
dc.identifier.scopusid | 2-s2.0-79952534509 | - |
dc.identifier.wosid | 000288202400008 | - |
dc.identifier.bibliographicCitation | ONCOGENE, v.30, no.10, pp.1213 - 1228 | - |
dc.relation.isPartOf | ONCOGENE | - |
dc.citation.title | ONCOGENE | - |
dc.citation.volume | 30 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 1213 | - |
dc.citation.endPage | 1228 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.subject.keywordPlus | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject.keywordPlus | HUMAN PROSTATE-CANCER | - |
dc.subject.keywordPlus | HYPOXIA-INDUCIBLE FACTOR-1 | - |
dc.subject.keywordPlus | MESSENGER-RNA STABILITY | - |
dc.subject.keywordPlus | FACTOR GENE-EXPRESSION | - |
dc.subject.keywordPlus | RENAL-CELL CARCINOMA | - |
dc.subject.keywordPlus | FACTOR-BETA | - |
dc.subject.keywordPlus | CYCLOOXYGENASE-2 EXPRESSION | - |
dc.subject.keywordPlus | HIF-2-ALPHA EXPRESSION | - |
dc.subject.keywordPlus | FACTOR (HIF)-1-ALPHA | - |
dc.subject.keywordAuthor | TGF-beta 1 | - |
dc.subject.keywordAuthor | VEGF | - |
dc.subject.keywordAuthor | Smad3 | - |
dc.subject.keywordAuthor | HIF-2 alpha | - |
dc.subject.keywordAuthor | HuR | - |
dc.subject.keywordAuthor | prostate cancer | - |
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