| http://purl.uniprot.org/citations/12958148 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12958148 | http://www.w3.org/2000/01/rdf-schema#comment | "Growing evidence indicates that inflammation is a contributing factor leading to cancer development. However, pathways involved in this progression are not well understood. To examine whether HIF-1alpha is a factor linking inflammation and tumorigenesis, we investigated whether the HIF-1 signaling pathway was stimulated by the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in A549 cells. We find that IL-1beta up-regulated HIF-1alpha protein under normoxia and activated the HIF-1-responsive gene vascular endothelial growth factor (VEGF) via a pathway dependent on nuclear factor kappaB (NFkB). Interestingly, although this pathway is stimulated by upstream signaling via AKT and mTOR and requires new transcription, IL-1 mediated HIF-1alpha induction also utilizes a post-transcriptional mechanism that involves antagonism of VHL-dependent HIF-1alpha degradation, which results in increased HIF-1alpha protein stability. IL-1 mediated NFkB-dependent cyclooxygenases-2 (COX-2) expression served as a positive effector for HIF-1alpha induction. Although COX-2 inhibitors attenuated IL-1 mediated HIF-1alpha induction, prostaglandin E2 (PGE2), a physiological product of COX-2, induced HIF-1alpha protein in a dose-dependent manner. Our data, therefore, demonstrate that IL-1beta up-regulates functional HIF-1alpha protein through a classical inflammatory signaling pathway involving NFkB and COX-2, culminating in up-regulation of VEGF, a potent angiogenic factor required for tumor growth and metastasis. Thus, HIF-1 is identified as a pivotal transcription factor linking the inflammatory and oncogenic pathways."xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.org/dc/terms/identifier | "doi:10.1096/fj.03-0329fje"xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/author | "Lee S."xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/author | "Jung Y.J."xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/author | "Isaacs J.S."xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/author | "Trepel J."xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/author | "Neckers L."xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/name | "FASEB J"xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/pages | "2115-2117"xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/title | "IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis."xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://purl.uniprot.org/core/volume | "17"xsd:string |
| http://purl.uniprot.org/citations/12958148 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12958148 |
| http://purl.uniprot.org/citations/12958148 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/12958148 |
| http://purl.uniprot.org/uniprot/Q16665#attribution-1E544E125DED276C31D531A1B0C82775 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12958148 |
| http://purl.uniprot.org/uniprot/Q16665#attribution-A3F7D3DDA2C4A35AB3B7EA7C21D44780 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12958148 |
| http://purl.uniprot.org/uniprot/Q16665#attribution-E1D9259FAC5990AF36A8B9FD56EA3CB9 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12958148 |
| http://purl.uniprot.org/uniprot/P01584#attribution-A3F7D3DDA2C4A35AB3B7EA7C21D44780 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12958148 |
| http://purl.uniprot.org/uniprot/P01584#attribution-E1D9259FAC5990AF36A8B9FD56EA3CB9 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12958148 |
| http://purl.uniprot.org/uniprot/P19838#attribution-1E544E125DED276C31D531A1B0C82775 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12958148 |