Mutant p53 R270H induces invasion and metastasis of mouse intestinal tumor organoids through gain-of-function mechanism

Apc(D716) mutant mice develop benign intestinal adenoma, while Apc(D716) and p53 R270H compound mutant mice develop invasive adenocarcinoma in the intestine. We examined expression profile of tumor-derived organoids using Apc(D716), Apc(D716) p53 Null, Apc(D716) p53 R270H mutant mice by RNA sequencing, and identified mutant p53-induced gene set. Overall design: Total RNA was extracted from Apc(D716) p53(+/+) tumor organoids, Apc(D716) p53(flox/flox) tumor organoids, and Apc(D716) p53(M/M) tumor organoids. For each genotype, two mice were used and organoids were prepared independently. p53(flox) allele is null mutation, whereas p53(M) allele carrys R270H mutation. We used Illumina HiSeq 2500, and examined expression profiles.

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Nakayama M, Sakai E, Echizen K, Yamada Y, Oshima H, Han TS, Ohki R, Fujii S, Ochiai A, Robine S, Voon DC, Tanaka T, Taketo MM, Oshima M