Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis.

TitleAdministration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis.
Publication TypeJournal Article
Year of Publication1999
AuthorsMahmoud NN, Dannenberg AJ, Bilinski RT, Mestre JR, Chadburn A, Churchill M, Martucci C, Bertagnolli MM
JournalCarcinogenesis
Volume20
Issue2
Pagination299-303
Date Published1999 Feb
ISSN0143-3334
KeywordsAdenomatous Polyposis Coli, Adenomatous Polyposis Coli Protein, Animals, beta Catenin, Carcinogenicity Tests, Chenodeoxycholic Acid, Cholagogues and Choleretics, Cytoskeletal Proteins, Dinoprostone, Disease Models, Animal, Duodenal Neoplasms, Duodenum, Female, Mice, Trans-Activators
Abstract

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 Apc (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 E2 (PGE2) 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 PGE2 in duodenal tissue. These data suggest that unconjugated bile acids contribute to periampullary tumor formation in the setting of an Apc mutation.

DOI10.1093/carcin/20.2.299
Alternate JournalCarcinogenesis
PubMed ID10069468
Grant List1R29CA74162-01 / CA / NCI NIH HHS / United States
25435 / / PHS HHS / United States
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