Treating mice with the proteasome inhibitor bortezomib stabilized p53 in stem/progenitor cells of the intestine and stomach, in other proliferating tissues, and in intestinal tumors.
Mouse model studies have shown that one of these missense-type mutations, p53R270H (corresponding to human R273H), causes submucosal invasion of intestinal tumors, while the loss of wild-type p53 has a limited effect on the invasion process.
Genetic testing revealed the same TP53 mutation in tumor cells of the rectal adenocarcinoma and vulvar and endocervical lesions, demonstrating that the Paget cells originated from the same intestinal tumor.
Loss of Apc and the entire chromosome 18 but absence of mutations at the Ras and Tp53 genes in intestinal tumors from Apc1638N, a mouse model for Apc-driven carcinogenesis.