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

Abstract:

:The interaction between mutations in the tumor-suppressor genes Apc and p53 was studied in congenic mouse strains to minimize the influence of polymorphic 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. The genetic modifier Mom1 and the pharmacological agents piroxicam and difluoromethylornithine each reduced intestinal adenoma multiplicity in the absence 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 specificity and synergy.

authors

Halberg RB,Katzung DS,Hoff PD,Moser AR,Cole CE,Lubet RA,Donehower LA,Jacoby RF,Dove WF

doi

10.1073/pnas.050585597

keywords:

subject

Has Abstract

pub_date

2000-03-28 00:00:00

pages

3461-6

issue

7

eissn

0027-8424

issn

1091-6490

pii

050585597

journal_volume

97

pub_type

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