期刊
JOURNAL OF ONCOLOGY
卷 2010, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2010/757908
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类别
资金
- Cancer Research UK
- Li Ka Shing Foundation
- Hutchison Whampoa Ltd
In cultured clear-cell renal carcinoma (CCRCC) 786-0 cells transfected with HIF1 alpha (HIF-1+), HIF-2 alpha (HIF-2+), or empty vector (EV), no significant differences were observed in the growth rates in vitro, but when grown in vivo as xenografts HIF2 alpha significantly increased, and HIF-1 alpha 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-2 alpha 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.
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