HIF-1α, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas
| العنوان: | HIF-1α, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas |
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| المؤلفون: | Michael J. Gray, Gregg L. Semenza, Douglas B. Evans, Jing Zhang, Gary E. Gallick, Stephanie S. Watowich, Lee M. Ellis |
| المصدر: | Oncogene. 24:3110-3120 |
| بيانات النشر: | Springer Science and Business Media LLC, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Male, Vascular Endothelial Growth Factor A, Cancer Research, Transcription, Genetic, chemistry.chemical_compound, Neoplasms, Gene expression, DNA-(Apurinic or Apyrimidinic Site) Lyase, Neoplasm Metastasis, Phosphorylation, Hypoxia, Luciferases, Promoter Regions, Genetic, STAT3, Regulation of gene expression, Neovascularization, Pathologic, Nuclear Proteins, Cobalt, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Vascular endothelial growth factor, src-Family Kinases, Female, Signal transduction, Tyrosine kinase, Protein Binding, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src, STAT3 Transcription Factor, Chromatin Immunoprecipitation, Immunoblotting, Enzyme-Linked Immunosorbent Assay, Biology, Cell Line, Tumor, Genetics, Humans, Immunoprecipitation, RNA, Messenger, Molecular Biology, Prostatic Neoplasms, Fibroblasts, Hypoxia-Inducible Factor 1, alpha Subunit, Enzyme Activation, Pancreatic Neoplasms, Microscopy, Fluorescence, chemistry, Trans-Activators, Cancer research, biology.protein, Autoradiography, Transcription Factors |
| الوصف: | Hypoxia stimulates a number of pathways critical to cancer cell survival, including the activation of vascular endothelial growth factor (VEGF) transcription. In normal fibroblasts, hypoxia-induced activation of the protein tyrosine kinase, Src, is required for VEGF expression. We show here in both pancreatic and prostate carcinoma cell lines cobalt chloride (used to mimic hypoxia) -induced VEGF expression requires Src activation and leads to increased steady-state levels of HIF-1alpha and increased phosphorylation of signal and transducer of transcription 3 (STAT3). STAT3 and hypoxia-inducible factor (HIF)-1alpha bind simultaneously to the VEGF promoter, where they form a molecular complex with the transcription coactivators CBP/p300 and Ref-1/APE. Expression of activated Src from an inducible promoter is sufficient to increase VEGF expression and form these STAT3/HIF-1alpha-containing promoter complexes. Inhibition of DNA binding by expression of either STAT3 or HIF-1alpha dominant negative mutants significantly reduces VEGF expression. These data suggest that the binding of both STAT3 and HIF-1alpha to the VEGF promoter is required for maximum transcription of VEGF mRNA following hypoxia. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f63d7bf4168b6d89109ff3d6b2ad3b14Test https://doi.org/10.1038/sj.onc.1208513Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f63d7bf4168b6d89109ff3d6b2ad3b14 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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