| Project/Area Number |
13470439
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Surgical dentistry
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
NAGUMO Masao Showa university, School of Dentistry, Professor, 歯学部, 教授 (70013993)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ITO Daisuke Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (40286844)
IWASE Masayasu Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (50193743)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 2002: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2001: ¥11,900,000 (Direct Cost: ¥11,900,000)
|
|---|
| Keywords | P53 deficient mouse / wild type mouse / carcinogen / P53 / p21 / oral leukoplakia / MDM2 / p53 independent pathway / 癌化 / ATM / 4NQO / 舌粘膜上皮 / 細胞周期 / Rb / E2F |
|---|
| Research Abstract |
p53 deficient mice (p53^<-/->) and wild type mice (WT) were treated with carcinogens, and their tongue tissues were examined histologically. Further, changes in the expression of mRNAs and protein of cell-cycle regulators and the phosphorylation of Rb were investigated. The correlation between the expression of ATM, p53 and MDM2 and epithelial dysplasia was also studied in human oral leukoplakia.
The results obtained were as follows :
1. Both in p53^<-/-> and WT mice, epithelial dysplasia such as thickening of the epithelial layer and loss of basal cell polarity were induced by the treatment of carcinogens and these changes become dominant with time.
2. In WT mice, the expression of p21 mRNA and its protein was increased by the treatment of carcinogens, whereas the expression of p21 was not increased by the treatment of carcinogens in p53^<-/-> mice. The expression of p53 in WT mice was increased 1 week after the treatment of carcinogens, but its expression was decreased 3 weeks after the treatment.
3. Phosphorylation of Rb protein was found in WT mice treated with carcinogens, though the amount of Rb protein was not changed. The expression of E2F was not also changed.
4. In oral leukoplakia, the expression of p53 becomes strong with the grade of epithelial dysplasia, but its expression in oral cancer become weaker. The correlation between ATM and epithelial dysplasia was not seen. The expression of MDM2 in oral leukoplakia was correlated with the grade of epithelial dysplasia, and its expression become stronger in oral cancer..
These results indicate that p53 dependent pathway may be concerned in the early stage of oral carcinogenesis and p53 independent pathway may participate in late stage of oral carcinogenesis.
|
