| Project/Area Number |
12794011
|
|---|
| Research Category |
Grant-in-Aid for University and Society Collaboration
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Hygiene
|
|---|
| Research Institution | Kyoto Prefectural University of Medicine |
|---|
Principal Investigator |
SAKAI Toshiyuki Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Professor, 医学部, 教授 (20186993)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Tatsushi Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Assistant Professor, 医学部, 助手 (80315936)
MATSUZAKI Youichirou Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Assistant Professor, 医学部, 助手 (70282522)
SOWA Yoshihiro Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Lecturer, 医学部, 講師 (70315935)
NOMURA Hitoshi Chugai Pharmaceutical Co.Ltd. Research Div., Senior Scientist, 創薬研究担当部長
KAMIYAMA Jun Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Assistant Professor, 医学部, 助手 (20257538)
高橋 千絵 京都府立医科大学, 医学部, 助手 (90305574)
加藤 満雄 京都府立医科大学, 医学部, 講師 (70260221)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥40,300,000 (Direct Cost: ¥40,300,000)
Fiscal Year 2002: ¥20,700,000 (Direct Cost: ¥20,700,000)
Fiscal Year 2001: ¥19,600,000 (Direct Cost: ¥19,600,000)
|
|---|
| Keywords | Vitamin D_3 / p27 / NF-Y / mac25 / gadd45 / Sodium Butyrate / flavonoids / quercetin / プロモーター / ヒストン脱アセチル化酵素阻害剤 / p21 / WAF1 / mac25遺伝子 / 癌 / 予防 / ビタミンD_3受容体 |
|---|
| Research Abstract |
We showed clearly that the vitamin D_3 which is considered to have a preventive effect on colon cancer and prostatic cancer, etc, contained in the mushroom used abundantly at the food of Kyoto, activates the p27 gene promoter through its Sp1 and CCAAT binding sites by the transcription factors Sp1 and NF-Y, and not through the vitamin D_3 receptor-binding site.
Vitamin D_3 also activates mac25, gene, which is known to compensate for the function of tumor-suppressor gene p53.
The dietary fiber, which is contained in the root crop used in the food of Kyoto, is metabolized to butyrate. We showed clearly that the butyrate activates the gadd45 gene promoter, in p53-independent manner, through its Oct-1 and CCAAT binding sites by the transcription factors Oct-1 and NF-Y.
We searched for another drugs which can activate gadd45 gene promoter from the ingredients of food, such as flavonoids contained in the Kyoto vegetable, green tea, etc., and found that quercetin which is a kind of flavonoid activates gadd45 gene in p53-independent manner. Although this activation was seen in the mRNA level, there was no change in promoter activity. It has suggested that the mechanism of activation of gadd45 gene is different between butyrate and quercetin.
Using about 16 gene promoters we have (eg. cell cycle-regulating genes, apoptosis related genes), the promoter-activating drug was searched and some interesting drugs were found out. These drugs are expected to become new cancer preventive drugs.
|
