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.
References
Cooks, T. et al. Mutant p53 prolongs NF-κB activation and promotes chronic inflammation and inflammation-associated colorectal cancer. Cancer Cell 23, 634–646 (2013)
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McCarthy, N. Mutant p53 fans the flames. Nat Rev Cancer 13, 441 (2013). https://doi.org/10.1038/nrc3553
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DOI: https://doi.org/10.1038/nrc3553