Action of Min and Mom1 on neoplasia in ectopic intestinal grafts.

Mice heterozygous for Min, a mutant allele of Apc, develop adenomas throughout the intestinal tract. Tumor multiplicity in Min mice is influenced by genetic modifier loci. Previously, we mapped one of these modifier loci, Mom1, to distal mouse chromosome 4. Mom1 is a semidominant modifier of both tumor size and multiplicity in Min mice. Recent evidence suggests that Mom1 may encode a secretory phospholipase, Pla2g2a. Pla2g2a is expressed in a variety of cell types and seems to be involved in inflammatory responses and bacterial defense mechanisms. Here, we determine whether Min and Mom1 act in a tissue-autonomous fashion using ectopic intestinal isografts. Within the small intestinal grafts, both Min and Mom1 act in a tissue-autonomous manner. There is no evidence that either Min or Mom1 has a systemic effect on tumor development. However, within the colonic grafts, the Min phenotype does not appear to be autonomous; the development of colonic tumors in Min mice seems dependent on factors beyond the Min genotype of the colonic epithelium. Micro-environmental factors, such as digestive secretions, dietary components, or intestinal flora, may be critical factors contributing to the development of Min-induced colonic tumors. However, these factors are not required for the action of Min or Mom1 within the small intestine.