Further evidence supporting NF-kB to directly activate PUMA in a p53 independent manner comes from a study by Wang et al. [38] where TNF-α stimulation of p53 mutant, p53 wild type or p53 knock out colorectal cancer cells lead to PUMA mRNA and protein upregulation via transcriptional activation of NF-kB. This evidence concerns the gene BBC3 and colorectal cancer.