| Project/Area Number |
15209070
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Showa University |
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Principal Investigator |
NAGUMO Masao Showa University, School of Dentistry, Professor, 歯学部, 教授 (70013993)
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| Co-Investigator(Kenkyū-buntansha) |
IWASE Masayasu Showa University, School of Dentistry, Assist Professor, 歯学部, 講師 (50193743)
ITO Daisuke Showa University, School of Dentistry, Assist Professor, 歯学部, 講師 (40286844)
KAMIJO Ryutaro Showa University, School of Dentistry, Professor, 歯学部, 教授 (70233939)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥40,170,000 (Direct Cost: ¥30,900,000、Indirect Cost: ¥9,270,000)
Fiscal Year 2005: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2004: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2003: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
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| Keywords | mouse / epithelial dysplasia / gene expression profile / oral leukoplakia / malignant transformation / kallikrein / cytokeratin / marker of malignant transformation / DNAチップ / 口腔癌 / 免疫染色 / 遺伝子プロファイル / 発癌剤 / マウス口腔粘膜 / 遺伝子発プロファイル / 前癌病変 / ヒト白板症 / 舌粘膜上皮 / 上皮異形成 |
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| Research Abstract |
To basically investigate changes in gene expression profiles during carcinogenesis, changes in gene expression profiles and morphological changes were examined in the tongue epithelial tissues of the mice after administrating carcinogens, 4NQO or benzo 【a】 pyrene. Further gene expression profiles were compared among human normal epithelia, oral leukoplakias and oral cancers using GeneChip system, and as to markedly up-regulated genes, their protein expression in those tissues was examined immunohistochemically.
The results obtained were as follows :
1) Epithelial dysplasia was observed in the tongue epithelia at 6 weeks after administration of carcinogens.
2) Expression of 63 genes was up-regulated, while that of 6 genes was down-regulated by the administration of carcinogens. Especially, characteristic changes were observed in SPRR2A, SPRR2E, SPRR2B and SPRR3 genes. Of these genes up-regulation of SPRR2A mRNA was confirmed by RT-PCR method.
3) In oral leukoplakia, 8 genes were up-regulated and 10 genes were down-regulated when compared with normal epithelial tissues. Of these genes, loricrin, keratin 2E and keratin10 genes were markedly down-regulated in oral cancer tissues.
4) In cases developing cancers from oral leukoplakias, gene expression in cancer tissues of loricrin, karatin10 and kallikrein was markedly down-regulated in comparison with oral leukoplakias.
5) Immunohistochemical examination revealed that expression of keratin10 protein was markedly decreased and it was only localized at the center of cancer lobules.
6) Kallikrein protein was also slightly localized at the center of cancer lobules.
These results indicates that changes in loricrin, karatin10 and kallikrein may be predictive markers of malignant transformation from oral leukoplakia. Analysis of gene polymorphism (SNP) is now undergoing and SNPs responsible for malignant transformation were not yet determined.
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