| Project/Area Number |
10470097
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
SAKAI Toshiyuki Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Professor, 医学部, 教授 (20186993)
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| 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 Yoshihirio Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Lecturer, 医学部, 講師 (70315935)
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| Project Period (FY) |
1998 – 2001
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| Keywords | p21 / WAF1 / gadd45 / cancer / p53 / prevention / promoter / p27 / histone deacetylase inhibitor |
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| Research Abstract |
1. p27 is a crucial tumor-suppressor gene. Vitamin D3 (VD3) activated p27 via promoter region and repressed cell growth. VD3 stimulated transcription of the p27 by a novel mechanism involving Sp1 and NF-Y, but not the VD3 receptor. These results indicate that we could develop a new drug without side effect such as hypercalcemia mediated by the VD3 receptor.
2. Butyrate, a dietay fiber metabolite, activated p21/WAF1 and acted as histone deacetylase (HDAC) inhibitor. We previously reported that butyrate activated p21/WAF1 by Sp1 and Sp3 through Sp1 site of the promoter. Moreover, butyrate activated gadd45 causing cell-cycle arrest and DNA repair. This activation is mediated through Oct-1 box and CCAAT box. p21/WAF1 and gadd45 are regulated by p53. p53 is critical factor in Li-Fraumeni syndrome and is inactivated in a half of malignancies. HDAC inhibitors which activate p21/WAF1 and gadd45 mght be preventive against patient of Li-Fraumeni syndrome or common cancer.
3. p16 as well as p53 is a gene inactivated in a half of malignancies. The promoter regions of p16 gene, p15-family genes (p15, p18 and p19) and p53-regulated genes (BAX, DR5, Sian-1 and PUMA) were cloned. We screened drugs activating these genes via these promoter regions and found intersting regulators. These regulators may become novel drugs for prevention of specific cancer.
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