p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway
- Author
- Morvarid Farhang Ghahremani (UGent) , Steven Goossens (UGent) , D Nittner, X Bisteau, Sona Bartunkova (UGent) , A Zwolinska, Paco Hulpiau (UGent) , Katharina Haigh (UGent) , Lieven Haenebalcke (UGent) , Benjamin Drogat (UGent) , A Jochemsen, PP Roger, Jean-Christophe Marine (UGent) and Jody Haigh (UGent)
- Organization
- Abstract
- There is growing evidence that the p53 tumour suppressor downregulates vascular endothelial growth factor (VEGF) expression, although the underlying mechanisms remain unclear and controversial. Here we provide insights from in vitro experiments and in vivo xenotransplantation assays that highlight a dual role for p53 in regulating VEGF during hypoxia. Unexpectedly, and for the first time, we demonstrate that p53 rapidly induces VEGF transcription upon hypoxia exposure by binding, in an HIF-1 alpha-dependent manner, to a highly conserved and functional p53-binding site within the VEGF promoter. However, during sustained hypoxia, p53 indirectly downregulates VEGF expression via the retinoblastoma (Rb) pathway in a p21-dependent manner, which is distinct from its role in cell-cycle regulation. Our findings have important implications for cancer therapy, especially for tumours that harbour wild-type TP53 and a dysfunctional Rb pathway.
- Keywords
- angiogenesis, p21, p53, VEGF, HYPOXIA-INDUCIBLE FACTOR, GROWTH-FACTOR GENE, WILD-TYPE P53, FACTOR-BINDING SITES, TUMOR ANGIOGENESIS, FACTOR 1-ALPHA, CELL-CYCLE, RETINOBLASTOMA, TRANSCRIPTION, PHOSPHORYLATION
Downloads
-
(...).pdf
- full text
- |
- UGent only
- |
- |
- 1.55 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-4101482
- MLA
- Farhang Ghahremani, Morvarid, et al. “P53 Promotes VEGF Expression and Angiogenesis in the Absence of an Intact P21-Rb Pathway.” CELL DEATH AND DIFFERENTIATION, vol. 20, no. 7, 2013, pp. 888–97, doi:10.1038/cdd.2013.12.
- APA
- Farhang Ghahremani, M., Goossens, S., Nittner, D., Bisteau, X., Bartunkova, S., Zwolinska, A., … Haigh, J. (2013). p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway. CELL DEATH AND DIFFERENTIATION, 20(7), 888–897. https://doi.org/10.1038/cdd.2013.12
- Chicago author-date
- Farhang Ghahremani, Morvarid, Steven Goossens, D Nittner, X Bisteau, Sona Bartunkova, A Zwolinska, Paco Hulpiau, et al. 2013. “P53 Promotes VEGF Expression and Angiogenesis in the Absence of an Intact P21-Rb Pathway.” CELL DEATH AND DIFFERENTIATION 20 (7): 888–97. https://doi.org/10.1038/cdd.2013.12.
- Chicago author-date (all authors)
- Farhang Ghahremani, Morvarid, Steven Goossens, D Nittner, X Bisteau, Sona Bartunkova, A Zwolinska, Paco Hulpiau, Katharina Haigh, Lieven Haenebalcke, Benjamin Drogat, A Jochemsen, PP Roger, Jean-Christophe Marine, and Jody Haigh. 2013. “P53 Promotes VEGF Expression and Angiogenesis in the Absence of an Intact P21-Rb Pathway.” CELL DEATH AND DIFFERENTIATION 20 (7): 888–897. doi:10.1038/cdd.2013.12.
- Vancouver
- 1.Farhang Ghahremani M, Goossens S, Nittner D, Bisteau X, Bartunkova S, Zwolinska A, et al. p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway. CELL DEATH AND DIFFERENTIATION. 2013;20(7):888–97.
- IEEE
- [1]M. Farhang Ghahremani et al., “p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway,” CELL DEATH AND DIFFERENTIATION, vol. 20, no. 7, pp. 888–897, 2013.
@article{4101482, abstract = {{There is growing evidence that the p53 tumour suppressor downregulates vascular endothelial growth factor (VEGF) expression, although the underlying mechanisms remain unclear and controversial. Here we provide insights from in vitro experiments and in vivo xenotransplantation assays that highlight a dual role for p53 in regulating VEGF during hypoxia. Unexpectedly, and for the first time, we demonstrate that p53 rapidly induces VEGF transcription upon hypoxia exposure by binding, in an HIF-1 alpha-dependent manner, to a highly conserved and functional p53-binding site within the VEGF promoter. However, during sustained hypoxia, p53 indirectly downregulates VEGF expression via the retinoblastoma (Rb) pathway in a p21-dependent manner, which is distinct from its role in cell-cycle regulation. Our findings have important implications for cancer therapy, especially for tumours that harbour wild-type TP53 and a dysfunctional Rb pathway.}}, author = {{Farhang Ghahremani, Morvarid and Goossens, Steven and Nittner, D and Bisteau, X and Bartunkova, Sona and Zwolinska, A and Hulpiau, Paco and Haigh, Katharina and Haenebalcke, Lieven and Drogat, Benjamin and Jochemsen, A and Roger, PP and Marine, Jean-Christophe and Haigh, Jody}}, issn = {{1350-9047}}, journal = {{CELL DEATH AND DIFFERENTIATION}}, keywords = {{angiogenesis,p21,p53,VEGF,HYPOXIA-INDUCIBLE FACTOR,GROWTH-FACTOR GENE,WILD-TYPE P53,FACTOR-BINDING SITES,TUMOR ANGIOGENESIS,FACTOR 1-ALPHA,CELL-CYCLE,RETINOBLASTOMA,TRANSCRIPTION,PHOSPHORYLATION}}, language = {{eng}}, number = {{7}}, pages = {{888--897}}, title = {{p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway}}, url = {{http://doi.org/10.1038/cdd.2013.12}}, volume = {{20}}, year = {{2013}}, }
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: