Targeted Deletion of p53 in Lgr5-Expressing Intestinal Stem Cells Promotes Colon Tumorigenesis in a Preclinical Model of Colitis-Associated Cancer.

ABSTRACT: p53 has been shown to mediate cancer stem-like cell function by suppressing pluripotency and cellular dedifferentiation. However, there have been no studies to date that have addressed the specific effects of p53 loss in colonic adult stem cells. In this study, we investigated the consequences of conditionally ablating p53 in the highly relevant Lgr5(+) stem cell population on tumor initiation and progression in the colon. In a mouse model of carcinogen (AOM)-induced colon cancer, tamoxifen-inducible Lgr5-driven deletion of p53 reduced apoptosis and increased proliferation of crypt stem cells, but had no effect on tumor incidence or size. Conversely, in a mouse model of colitis-associated cancer, in which mice are exposed to AOM and the potent inflammation inducer DSS, stem cell-specific p

SUBMITTER: Davidson LA 

PROVIDER: S-EPMC4681667 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature