| Project/Area Number |
08457474
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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 |
Morphological basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TSUCHIDA N. Tokyo Med & Dent Univ, Fac of Dent, Professor, 歯学部, 教授 (60089951)
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| Co-Investigator(Kenkyū-buntansha) |
MUNIRAJAN A.K. Tokyo Med & Dent Univ, Fac of Dent, Research Asso., 歯学部, 教務職員 (10291345)
IRITANI A. Tokyo Med & Dent Univ, Fac of Dent, Research Asso., 歯学部, 教務職員 (20292972)
AMAGASA T. Tokyo Med & Dent Univ, Fac of Dent, Professor, 歯学部, 教授 (00014332)
ENOMOTO S. Tokyo Med & Dent Univ, Fac of Dent, Professor, 歯学部, 教授 (40013940)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | p53 / H-ras / G2 / M / HSP70 / transformation / transrepresson / temperature sensitive / N-ras / 癌抑制遺伝子 / 口腔癌 / 温度感受性変異株 / differantial display / ras / ゲルシフトアッセイ / トランスフォーメーション抑制能 / 転写活性 / p130 |
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| Research Abstract |
(Purpose) To investigate molecular mechanisms of the genesis of oral squamouss cell carcinomas (SCCs), we (1) looked for factors involved in the genesis of oral SCCs in Japan and India by analyzing alterations of tumor suppressor genes and oncogenes and also (2) studied the roles of mutant p53 found in oral SCC.
(Results) (1) Ras gene mutations among 46 patientss analyzed in India ; , we identified 6 H-ras and one N-ras mutations by DNA sequencing, and 2 additional sample by PCR/SCP.One novel mutaion (H-ras codon 59) was found. p53 mutations were newly analyzed for SCCs of India and was mostly G>T,G>A mutatins, sugesting close relation to tabaco chewing as etiologic factor. (2) Functional analysis of mutant p53. A 149pro mutation : Biologically the mutant funcitoned as wild type in transformation-suppression and colony formation assays. Biochemically the mutant transreppressed HSP70 promoter acitivity at low temperature, but activated at high temperature. But these activities were less pronounced for other promoters (SV40, and polymerase beta). B.Saos-2 cells carrying 220His or 285lys mutations which were originally identified in oral SCCs were temperature sensitive. Growth arrest in G1 and G2/M stages was ovserved like in cells carrying 138Val. We tried to isolate p53 downstream effectors expressed in G2/M phase by differential display. Three DNA fragments were islated. One of them was BTG2 which had been suggested to be involved in cell cycle control of G2/M phase.
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