Mutations in the tumour suppressor protein p53 do not always result in a loss of function; some mutants have a gain of function (GOF). Moshe Oren and colleagues found that expression of the R273H p53 GOF mutant in a pancreatic cancer cell line resulted in the prolonged expression of tumour necrosis factor and the activation of nuclear factor-κB (NF-κB). In mouse models of inflammation-mediated colorectal cancer, expression of R273H p53 in the mouse colon resulted in chronic inflammation and the development of invasive cancer. This progression mimicked that seen in patients with colitis-associated colorectal cancer in which mutation of p53 is an early event.