TY - JOUR
TI - Mutant p53 Prolongs NF-κB Activation and Promotes Chronic Inflammation and Inflammation-Associated Colorectal Cancer
AU - Cooks, T.
AU - Pateras, I.
AU - Tarcic, O.
AU - Solomon, H.
AU - Schetter, A.
AU - Wilder, S.
AU - Lozano, G.
AU - Pikarsky, E.
AU - Forshew, T.
AU - Rozenfeld, N.
AU - Harpaz, N.
AU - Itzkowitz, S.
AU - Harris, C.
AU - Rotter, V.
AU - Gorgoulis, V.
AU - Oren, M.
JO - Cancer Cell
PY - 2013
VL - 23
TODO - 5
SP - 634-646
PB - Cell Press
SN - null
TODO - 10.1016/j.ccr.2013.03.022
TODO - dextran sulfate;  immunoglobulin enhancer binding protein;  protein p53, article;  cell culture;  chromatin immunoprecipitation;  chronic inflammation;  colitis;  colorectal cancer;  disease association;  disease severity;  enzyme activation;  human;  human cell;  inflammation;  invasive carcinoma;  mouse;  nonhuman;  nucleotide sequence;  priority journal;  real time polymerase chain reaction;  tissue injury
TODO - The tumor suppressor p53 is frequently mutated in human cancer. Common mutant p53 (mutp53) isoforms can actively promote cancer through gain-of-function (GOF) mechanisms. We report that mutp53 prolongs TNF-α-induced NF-κB activation in cultured cells and intestinal organoid cultures. Remarkably, when exposed to dextran sulfate sodium, mice harboring a germline p53 mutation develop severe chronic inflammation and persistent tissue damage, and are highly prone to inflammation-associated colon cancer. This mutp53 GOF is manifested by rapid onset of flat dysplastic lesions that progress to invasive carcinoma with mutp53 accumulation and augmented NF-κB activation, faithfully recapitulating features frequently observed in human colitis-associated colorectal cancer (CAC). These findings might explain the early appearance of p53 mutations in human CAC. © 2013 Elsevier Inc.
ER -