These findings suggest that the anti-apoptotic function of pRb in ccRCC cells may be dependent on VHL or HIF expression, which is consistent with the differential transcriptional regulation by pRb in the presence or absence of VHL (Fig. 3D) and the synthetic lethality observed between Vhl and Rb1 [49]. This evidence concerns the gene RB1 and nonpapillary renal cell carcinoma.