Gould K A, Dove W F
McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, Madison, 53706, USA.
Cell Growth Differ. 1996 Oct;7(10):1361-8.
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.
Apc的突变等位基因Min的杂合子小鼠在整个肠道中都会发生腺瘤。Min小鼠的肿瘤多发性受遗传修饰位点影响。此前，我们将其中一个修饰位点Mom1定位到小鼠4号染色体远端。Mom1是Min小鼠肿瘤大小和多发性的半显性修饰基因。最近的证据表明，Mom1可能编码一种分泌型磷脂酶Pla2g2a。Pla2g2a在多种细胞类型中表达，似乎参与炎症反应和细菌防御机制。在这里，我们使用异位肠道同基因移植来确定Min和Mom1是否以组织自主的方式发挥作用。在小肠移植中，Min和Mom1均以组织自主的方式发挥作用。没有证据表明Min或Mom1对肿瘤发展有全身影响。然而，在结肠移植中，Min表型似乎不是自主的；Min小鼠结肠肿瘤的发展似乎依赖于结肠上皮Min基因型以外的因素。微环境因素，如消化分泌物、饮食成分或肠道菌群，可能是导致Min诱导的结肠肿瘤发生的关键因素。然而，这些因素对于Min或Mom1在小肠中的作用并非必需。
