Tumorigenesis in the multiple intestinal neoplasia mouse: Redundancy of negative regulators and specificity of modifiers

The interaction between mutations in the tumor-suppressor genes Ape and p53 was studied in congenic mouse strains to minimize the influence of polymor phic modifiers. The multiplicity and invasiveness of intestinal adenomas of Apc(Min/+) (Min) mice was enhanced by deficiency for p53, In addition, the occurrence of desmoid fibromas was strongly enhanced by p53 deficiency. Th e genetic modifier Mom1 and the pharmacological agents piroxicam and difluo romethylornithine each reduced intestinal adenoma multiplicity in the absen ce of p53 function. Mom1 showed no influence on the development of desmoid fibromas, whereas the combination of piroxicam and difluoromethylornithine exerted a moderate effect, The ensemble of tumor suppressors and modifiers of a neoplastic process can be usefully analyzed in respect to tissue speci ficity and synergy.