We demonstrate here that hypoxia-inducible factors -2a promotes cell-cycle progression in hypoxic renal clear cell carcinoma and multiple other cell lines
2007
Key concepts
- hypoxia
- von Hippel
- neoplastic progression
- von Hippel-Lindau
- carcinoma
- tumor cell
- phosphoglycerate kinase
- chromatin IP
- cell line
- fibroblasts
- cell cycle progression
- cyclin-dependent kinase inhibitor
- hypoxia-inducible factors
- vascular endothelial growth factor
- epithelial cells
- cyclin-dependent kinase 2
- initiator element
- ARNT
- clear cell
Scholarcy highlights
- Low oxygen levels are frequently encountered in solid tumors, and hypoxic stress responses have important effects on the natural history of disease
- hypoxia-inducible factors-2a was detected in HCT116 cells, but at approximately 10% the levels observed in WT8 cells
- To correlate these data with transcriptional targets, mRNA was extracted from cells grown at 21% or 0.5% O2 for 24, 48, and 72 hr and analyzed by quantitative real-time PCR
- While HCT116 cells exhibited basal Oct4 expression, hypoxic induction of HIF-2a in these cells had no further effect on transcript levels, likely due to low HIF-2a protein levels
- We found that HIF-2a promotes c-Myc transcriptional activity and cell-cycle progression in renal carcinoma cells, NIH3T3 cells, HEK293 cells, and embryonic epithelial cells
- When the WT8 cells were grown at 0.5% O2, statistically significant increases in the percentage of cells in S phase and decreases in the percentage in G1 phase after 24, 48, or 72 hr were observed
- HIF-2a activation of these targets is not responsible for transformation in our study, as Oct4 and TGF-a were not detected in transformed mouse embryo fibroblasts cell lines or NIH3T3 cells described above, and similar mRNA and protein levels were observed for Cyclin D1 regardless of HIF-a expression
- Enhanced c-Myc activity likely contributes to hypoxia-inducible factors-2a-mediated neoplastic progression following loss of the von Hippel-Lindau tumor suppressor and influences the behavior of hypoxic tumor cells
Need more features? Save interactive summary cards to your Scholarcy Library.