Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis
Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis
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DOI：
10.1093/carcin/20.2.299
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发表时间：
1999-02-01
期刊：
影响因子：
4.7
通讯作者：
Bertagnolli, MM
中科院分区：
文献类型：
--
作者：
Mahmoud, NN;Dannenberg, AJ;Bertagnolli, MM
Intestinal carcinogenesis involves the successive accumulation of multiple genetic defects until cellular transformation to an invasive phenotype occurs. This process is modulated by many epigenetic factors. Unconjugated bile acids are tumor promoters whose presence in intestinal tissues is regulated by dietary factors. We studied the role of the unconjugated bile acid, chenodeoxycholate, in an animal model of familial adenomatous polyposis. Mice susceptible to intestinal tumors as a result of a germline mutation in Ape (Min/+ mice) were given a 10 week dietary treatment with 0.5% chenodeoxycholate. Following this, the mice were examined to determine tumor number, enterocyte proliferation, apoptosis and beta-catenin expression. Intestinal tissue prostaglandin E-2 (PGE(2)) levels were also assessed. Administration of chenodeoxycholate in the diet increased duodenal tumor number in Min/+ mice. Promotion of duodenal tumor formation was accompanied by increased beta-catenin expression in duodenal cells, as well as increased PGE(2) in duodenal tissue. These data suggest that unconjugated bile acids contribute to periampullary tumor formation in the setting of an Apc mutation.
