2007 Fiscal Year Final Research Report Summary
Role of the dioxin receptor E3 ubiquitin ligase in suppression of cecal carcinogenesis
| Project/Area Number |
16390036
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Environmental pharmacy
|
|---|
| Research Institution | Research Institute for Clinical Oncology, Saitama Cancer Center |
|---|
Principal Investigator |
KANAME Kawajiri Research Institute for Clinical Oncology, Saitama Cancer Center, Research Division, Chief (50142112)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IKUTA Togo Saitama Cancer Center, Research Division (00262072)
|
|---|
| Project Period (FY) |
2004 – 2007
|
| Keywords | AhR / Colorectal cancer / Tumor suppression / β-catenin / E3 ubicluitin ligase / APC / Auxin / Inflammation |
|---|
| 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.
|
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Mechanisms of Tocicological and Physioiogical Actions of Arylhydrocarbon Receptor (AhR) in Mice.2007
Author(s)
Fujii-Kuriyama, Y., Mimura, J., Baba, T., Morohashi, K., Ohtake, F., Kato, S., Kobayashi, Y., Kawajiri, K.
Organizer
Dioxin 2007 International Symposium,
Place of Presentation
Japan(Tokyo)
Year and Date
20070900
Description
「研究成果報告書概要(和文)」より
-
[Presentation] Mechanisms of Tocicological and Physioiogical Actions of Arylhydrocarbon Receptor(AhR) in Mice.2007
Author(s)
Fujii-Kuriyama, Y., Mimura, J., Baba, T., Morohashi, K., Ohtake, F., Kato, S., Kobayashi, Y., Kawajiri, K.
Organizer
Dioxin 2007 International Symposium
Place of Presentation
Japan(Tokyo)
Year and Date
20070900
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Presentation] Spontaneous development of colon cancer in aryl hydrocarbon receptor-deficient mouse.2007
Author(s)
Kawajiri, K., Kobayashi, Y., Ikuta, T., Matsushima, Y., Mimura, J., Kurozumi, M., Fujii-Kuriyama, Y.
Organizer
The 6th SORST Joint Symposium Jan.
Place of Presentation
Japan(Tokyo)
Year and Date
20070000
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
-
-
-
