However, in vitro studies on ccRCC cell lines A498 and 786-0 suggested that the reduction of RKIP in tumour cells is at least in part mediated by the methylation of the RKIP promoter which represses its expression; On the contrary, the demethylation of the RKIP promoter increases its levels both as mRNA and protein. This evidence concerns the gene PEBP1 and nonpapillary renal cell carcinoma.