GENES CONTROLLING NEOPLASIA OF THE INTESTINAL EPITHELIUM

University Of Wisconsin Madison, Madison WI

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Abstract

The Min mouse strain develops multiple intestinal neoplasms on sensitive genetic background. It is heterozygous for a nonsense allele of the Adenomatous polyposis coli gene of the mouse, Apc. We first shall aim to settle controversial issues concerning the strict adherence of adenoma formation to the one-locus Knudson model and the clonality of early tumors. Then, we shall explore the involvement of several candidate molecular systems in the Min phenotype, including the Wingless signaling pathway. Our work culminates in developing a sensitized genetic screen for mutant modifiers of the Min phenotypes. This screen, novel in mammalian cancer genetics, may identify a series of factors acting in this tumor lineage and in the tumor-bearing host.