Abstract
In cultured clear-cell renal carcinoma (CCRCC) 786-0 cells transfected with HIF1α (HIF-1+), HIF-2α (HIF-2+), or empty vector (EV), no significant differences were observed in the growth rates in vitro, but when grown in vivo as xenografts HIF-2α significantly increased, and HIF-1α significantly decreased growth rates, compared to EV tumors. Factors associated with proliferation were increased and factors associated with cell death were decreased in HIF-2+ tumors. Metabolite profiles showed higher glucose and lower lactate and alanine levels in the HIF-2+ tumors whilst immunostaining demonstrated higher pyruvate dehydrogenase and lower pyruvate dehydrogenase kinase 1, compared to control tumors. Taken together, these results suggest that overexpression of HIF-2α in CCRCC 786-0 tumors regulated growth both by maintaining a low level of glycolysis and by allowing more mitochondrial metabolism and tolerance to ROS induced DNA damage. The growth profiles observed may be mediated by adaptive changes to a more oxidative phenotype.
DOI
10.1155/2010/757908
Publication Date
2010-01-01
Publication Title
Journal of Oncology
Volume
2010
Publisher
Hindawi Limited
ISSN
1687-8469
Embargo Period
2024-11-19
First Page
1
Last Page
14
Recommended Citation
Biswas, S., Troy, H., Leek, R., Chung, Y., & et al. (2010) 'Effects of HIF-1 and HIF2 on Growth and Metabolism of Clear-Cell Renal Cell Carcinoma 786-0 Xenografts', Journal of Oncology, 2010, pp. 1-14. Hindawi Limited: Available at: https://doi.org/10.1155/2010/757908
