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Abstract
Hypoxia inducible factor (HIF) is the major transcription factor involved in the regulation of the cellular response to hypoxia or low oxygen tensions. Even though HIF-1 function is mostly studied following hypoxic stress, well oxygenated areas of several diseased tissues have detectable levels of this transcription factor. Therefore, it is surprising how little is known about the function of HIF in normoxia. This study seeks to fill this gap. Using transient HIF-1 alpha knockdown, as well as, stable cell lines generated using short hairpin RNAs (shRNA), we have further characterized the role of HIF-1 alpha in normoxia. Our data reveals that knockdown of HIF-1 alpha results in a significant increase in cells in the G 1 phase of the cell cycle. We find that HIF-1 alpha depletion increases the protein and mRNA of both p21 and p27. p21 is induced via, at least in part, p53-independent but SP1-dependent mechanisms. Interestingly, HIF-1 alpha knockdown also alters the cellular response to chemotherapeutic agents. These data have important implications in not only for the further understanding of HIF-1 alpha, a major transcription factor, but also for the use of HIF-targeted and combination therapies in cancer treatment.
Original language | English |
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Pages (from-to) | 1249-1260 |
Number of pages | 12 |
Journal | Cell Cycle |
Volume | 10 |
Issue number | 8 |
DOIs | |
Publication status | Published - 15 Apr 2011 |
Keywords
- HIF-1
- p21
- p27
- SP1
- cell cycle
- HYPOXIA-INDUCIBLE FACTOR
- NF-KAPPA-B
- ENDOTHELIAL GROWTH-FACTOR
- CDK-INHIBITOR P21(WAF1/CIP1)
- HIPPEL-LINDAU PROTEIN
- FACTOR 1-ALPHA
- TUMOR-SUPPRESSOR
- UNFAVORABLE PROGNOSIS
- INDUCED APOPTOSIS
- FACTOR-1-ALPHA EXPRESSION
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- 1 Finished
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Aref#d: 19770. Division of Gene Regulation and Expression Strategic Award
Blow, J., Hutvagner, G., Lamond, A., Owen-Hughes, T. & Swedlow, J.
1/01/08 → 31/12/12
Project: Research