Previous studies which have interpreted the oncogenic and tumour suppressive roles of HIF-α factors in ccRCC based on studies of cultured ccRCC cells and xenograft models may therefore not necessarily be reflective of the true in vivo functions of HIF-1α and HIF-2α at different stages of tumour development in the physiological context of the kidney. This evidence concerns the gene HIF1A and nonpapillary renal cell carcinoma.