The effects of CDK inhibitors and PI3 kinase related kinase on the carcinogenesis from precancerous lesions
| Project/Area Number |
11470443
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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 |
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) |
YUI Kumie Showa university, School of Dentistry, Lecturer, 歯学部, 助手 (50317583)
HATORI Masashi Showa university, School of Dentistry, Assistant Professor, 歯学部, 講師 (20245814)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥9,400,000 (Direct Cost: ¥9,400,000)
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| Keywords | oral leukoplakia / carcinogenesis / MDM2 / ATM / CDK inhibitors / p21 / p53 gene deficient mouse / 4NQO / DNA-PK / P21 / P53遺伝子欠失マウス / mRNA |
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| Research Abstract |
We investigated the expression of MDM2 and PI3 kinase related kinase proteins in cases with oral leukoplakia and oral cancer, and normal epithelium. Further, changes in the gene expression of INK4 and p21 families was examined in oral keratinocytes of p53 knockout and wild mice.
The results obtained were as follows :
1. The expression of MDM2 in oral leukoplakia was correlated with the grade of epithelial dysplasia, whereas that in oral cancer was weaker than that in oral leukoplakia with severe dysplasia. The expression of p21, a CDK inhibitor, was found in oral leukoplakias with moderate and severe epithelial dysplasia. However, it was not observed in normal epithelia and cancer tissues.
2. PI3 kinase related kinases (ATM, ATR, DNA-PK) were expressed in the cytoplasm of whole epithelial cells.
3. At 10 days after 4NQO administration, oral keratinocytes were obtained from mouse tongue or palate and the gene expression of CDK inhibitors was analyzed by RT-PCR method. The results revealed that p21 and p27 mRNAs were induced in keratinocytes of wild mice, but that they were not induced in those of p53 knockout mice.
4. Cyclin D, CDK4 and p16 mRNAs were induced by 4NQO treatment in keratinocytes of wild mice.
These results indicate that stimulation for carcinogenesis not only induces cell proliferating factors such as Cyclin and CDK, but also induces the CDK inhibitor genes which suppress cell proliferation.
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Report
(2 results)
Research Products
(16 results)
