2010 Fiscal Year Final Research Report
Retinoic acid metabolizing enzyme CYP26A1 is a candidate oncogene, and a possible therapeutic target for cancers.
| Project/Area Number |
20590402
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kochi University |
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Principal Investigator |
OSANAI Makoto Kochi University, 教育研究部・医療学系, 准教授 (60381266)
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| Co-Investigator(Renkei-kenkyūsha) |
LEE Gang-Hong 高知大学, 教育研究部・医療学系, 教授 (10261405)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 腫瘍 / 発癌 / レチノイン酸 / ビタミンA / 癌遺伝子 |
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| Research Abstract |
Vitamin A deficiency (VAD) is associated with increased susceptibility to carcinogenesis in animal models and elevated risk for a number of human cancers. We found that the CYP26A1, the gene encoding a cytochrome P450 enzyme specifically involved in metabolic inactivation of retinoic acid (RA), the most active vitamin A derivative, is highly expressed in a number of variety types of cancer, including primary breast carcinomas. We also found that the state of reduced RA bioavailability caused by enhanced expression of CYP26A1 is sufficient to markedly increase tumorigenic and metastatic potential. Our observations provide strong evidence for oncogenic and cell survival properties of CYP26A1 in carcinogenesis, and suggest mechanisms whereby VAD might promote cancer development. We believe that specific drug-mediated inactivation of CYP26A1 may have a notable impact on malignant potential of human tumors, and these results show its potential feasibility of CYP26A1-inhibitory cancer therapies.
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[Journal Article] IGF-I regulates tight-junction protein claudin-1 during differentiation of osteoblast-like MC3T3-E1 cells via a MAP-kinase pathway.2008
Author(s)
Hatakeyama N, Kojima T, Iba K, Murata M, Thi MM, Spray DC, Osanai M, Chiba H, Ishiai S, Yamashita T, Sawada N.
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Journal Title
Cell Tissue Res 334
Pages: 243-254
Peer Reviewed
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[Journal Article] Transforming growth factor-beta induces epithelial to mesenchymal transition by down-regulation of claudin-1 expression and the fence function in adult rat hepatocytes.2008
Author(s)
Kojima T, Takano K, Yamaguchi H, Murata M, Son S, Imamura M, Yamaguchi H, Osanai M, Chiba H, Himi T, Sawada N.
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Journal Title
Liver Int 28
Pages: 534-545
Peer Reviewed
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[Journal Article] Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation.2008
Author(s)
Koizumi J, Kojima T, Ogasawara N, Murata M, kamekura R, Kurose M, Go M, Harimaya A, Murata M, Osanai M, Chiba H, Himi T, Sawada N.
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Journal Title
Mol Pharmacol 74
Pages: 432-442
Peer Reviewed
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