MacPhee M, Chepenik K P, Liddell R A, Nelson K K, Siracusa L D, Buchberg A M
Department of Microbiology and Immunology, Jefferson Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Cell. 1995 Jun 16;81(6):957-66. doi: 10.1016/0092-8674(95)90015-2.
Mutations in the APC gene are responsible for various familial and sporadic colorectal cancers. Min mice carry a dominant mutation in the homolog of the Apc gene and develop multiple adenomas throughout their small and large intestine. Quantitative trait loci studies have identified a locus, Mom1, which maps to the distal region of chromosome 4, that dramatically modifies Min-induced tumor number. We report here the identification of a candidate gene for Mom1. The gene for secretory type II phospholipase A2 (Pla2s) maps to the same region that contains Mom1 and displays 100% concordance between allele type and tumor susceptibility. Expression and sequence analysis revealed that Mom1 susceptible strains are most likely null for Pla2s activity. Our results indicate that Pla2s acts as a novel gene that modifies polyp number by altering the cellular microenvironment within the intestinal crypt.
APC基因的突变是导致各种家族性和散发性结直肠癌的原因。Min小鼠在Apc基因的同源物中携带一个显性突变，并在其整个小肠和大肠中形成多个腺瘤。数量性状基因座研究确定了一个名为Mom1的基因座，它位于4号染色体的远端区域，该区域显著改变了Min诱导的肿瘤数量。我们在此报告Mom1候选基因的鉴定。分泌型II型磷脂酶A2（Pla2s）基因定位于包含Mom1的同一区域，并且在等位基因类型与肿瘤易感性之间显示出100%的一致性。表达和序列分析表明，Mom1易感菌株很可能缺乏Pla2s活性。我们的结果表明，Pla2s作为一个新基因，通过改变肠隐窝内的细胞微环境来改变息肉数量。
