| Budget Amount *help |
¥15,780,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2007: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥3,900,000 (Direct Cost: ¥3,900,000)
|
|---|
| Research Abstract |
The dioxin receptor (or aryl hydrocarbon receptor, AhR) is a ligand-dependent transcription factor known to be involved in the promotion of chemical carcinogenesis. Here we show that AhR (-/-) mice spontaneously develop adenocarcinomas mainly in the cecum with abnormal accumulation of f3-catenin. The mechanism of tumor suppression involves a novel AhR-mediated mechanism of ubiquitination and proteasomal degradation of β-catenin that works in parallel to the APC system. This function of AhR is activated by indole-3-acetic acid converted from dietary tryptophan by intestinal microbes. Germ-free AhR (1)mice did not develop tumors but remained in a cancer-prone state with accumulated. p-catenin, suggesting that loss of degradation of β-catenin in AhR (-/-) mice together with stimuli from intestinal microbes work co-operatively to cause tumor development.
|
