Effects of HIF-1 and HIF2 on growth and metabolism of clear-cell renal cell carcinoma 786-0 xenografts

In cultured clear-cell renal carcinoma (ccrcc) 786-0 cells transfected with hif1 (hif-1+),hif-2 (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-2 significantly increased,and hif-1 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 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. copyright © 2010 swethajit biswas et al.