Intestinal cancer progression by mutant p53 through the acquisition of invasiveness associated with complex glandular formation.

ABSTRACT: Tumor suppressor TP53 is frequently mutated in colorectal cancer (CRC), and most mutations are missense type. Although gain-of-functions by mutant p53 have been demonstrated experimentally, the precise mechanism for malignant progression in in vivo tumors remains unsolved. We generated Apc^Δ716 Trp53^LSL•R270H villin-CreER compound mice, in which mutant p53^R270H was expressed in the intestinal epithelia upon tamoxifen treatment, and examined the intestinal tumor phenotypes and tumor-derived organoids. Mutant Trp53^R270H, but not Trp53-null mutation accelerated submucosal invasion with generation of desmoplastic microenvironment. The nuclear accumulation of p53 was evident in Apc^Δ716 Trp53^R270H/R270H homozygous tumors like human

SUBMITTER: Nakayama M 

PROVIDER: S-EPMC5658682 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature