Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids

Carcinogenesis. 2015 Oct;36(10):1193-200. doi: 10.1093/carcin/bgv107. Epub 2015 Jul 25.


Although epidemiological evidence in humans and bile acid feeding studies in rodents implicate bile acids as tumor promoters, the role of endogenous bile acids in colon carcinogenesis remains unclear. In this study, we exploited mice deficient in the ileal apical sodium-dependent bile acid transporter (ASBT, encoded by SLC10A2) in whom fecal bile acid excretion is augmented more than 10-fold. Wild-type and Asbt-deficient (Slc10a2 (-/-) ) male mice were treated with azoxymethane (AOM) alone to examine the development of aberrant crypt foci, the earliest histological marker of colon neoplasia and a combination of AOM and dextran sulfate sodium to induce colon tumor formation. Asbt-deficient mice exhibited a 54% increase in aberrant crypt foci, and 70 and 59% increases in colon tumor number and size, respectively. Compared to littermate controls, Asbt-deficient mice had a striking, 2-fold increase in the number of colon adenocarcinomas. Consistent with previous studies demonstrating a role for muscarinic and epidermal growth factor receptor signaling in bile acid-induced colon neoplasia, increasing bile acid malabsorption was associated with M3 muscarinic and epidermal growth factor receptor expression, and activation of extracellular signal-related kinase, a key post-receptor signaling molecule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bile Acids and Salts / genetics
  • Bile Acids and Salts / metabolism
  • Bile Acids and Salts / toxicity*
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Feces
  • Humans
  • Ileum / metabolism*
  • Ileum / pathology
  • Mice
  • Mice, Knockout
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • Organic Anion Transporters, Sodium-Dependent / metabolism
  • Signal Transduction / drug effects
  • Symporters / genetics*
  • Symporters / metabolism


  • Bile Acids and Salts
  • Organic Anion Transporters, Sodium-Dependent
  • Symporters
  • sodium-bile acid cotransporter