IDO1 metabolites activate β-catenin signaling to promote cancer cell proliferation and colon tumorigenesis in mice.

ABSTRACT:

Background & aims

Indoleamine 2,3 dioxygenase-1 (IDO1) catabolizes tryptophan along the kynurenine pathway. Although IDO1 is expressed in inflamed and neoplastic epithelial cells of the colon, its role in colon tumorigenesis is not well understood. We used genetic and pharmacologic approaches to manipulate IDO1 activity in mice with colitis-associated cancer and human colon cancer cell lines.

Methods

C57Bl6 wild-type (control), IDO1-/-, Rag1-/-, and Rag1/IDO1 double-knockout mice were exposed to azoxymethane and dextran sodium sulfate to induce colitis and tumorigenesis. Colitis severity was assessed by measurements of disease activity, cytokine levels, and histologic analysis. In vitro experiments were conducted using HCT 116 and HT-29 human colon cancer cells. 1-methyl try

SUBMITTER: Thaker AI 

PROVIDER: S-EPMC3722304 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature