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Molecular mechanisms of genesis of oral squamous cell carcinoma

Research Project

Project/Area Number 08457474
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TSUCHIDA N.  Tokyo Med & Dent Univ, Fac of Dent, Professor, 歯学部, 教授 (60089951)

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)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
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)
Keywordsp53 / 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
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.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Munirajan AK, Tsuchida N. 他: "p53 gene mutations in oral ccarcinomasfrom India" Int.J.Cancer. 66. 297-300 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takada S, Tsuchida N. 他: "Hepatitis B viruus X gene expression is activated by X protein but repressed by p53 tumor suppressor gene product in the transientexpression system" Virology. 216. 80-89 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Komiya T, Tsuchida N. 他: "Comparison of DNA compy numbers in original oral squamous cell carcinomas and corresponding cell lines by comparative genomic hybridization" Jpn.J.Cancer Res.88. 476-483 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Akagi T, Tsuchida N. 他: "Aberrant expression and function of p53 in T-cells immortalized by HTLV-1 Taxl" FEBS Letters. 406. 263-266 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koizumi Y, Tsuchida N. 他: "Change in DNA copy number in primary gastric carcinomas by comparative genomic hybridization" Clinical Cancer Res.3. 1067-1076 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takada S, Tsuchida N. 他: "Cytoplasmic retention of the p53 tumorsuppressor gene product is observed in the hepatitis B virus X gene-transfected cells" Oncogene. 15. 1895-1901 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Komiyama T, Tsuchida N.他: "Comparison of DNA compy numbers in original oral squamous cell carcinomas and corresponding cell lines by comparative genomic hybridization" Jpn.J.Cancer Res.88. 476-483 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Akagi T, Tsuchida N.他: "Aberrant expression and function of p53 in T-cells immortalized by HTLV-l Taxl" FEBS Letters. 406. 263-266 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koizumi Y, Tsuchida N.他: "Change in DNA copy number in primary gastric carcinomas by comparative genomic hybridization" Clinical Cancer Res.3. 1067-1076 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takada S, Tsuchida N.他: "Cytoplasmic retention of the p53 tumor suppressor gene product is observed in the hepatitis B virus X gene-transfected cells" Oncogene. 15. 1895-1901 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Munirajan,A.K, Tsuchida N他: "The status of human papillomavirus and tumor suppressor genes p53 and p16 in carcinomas of uterine cervix from India" Gynecology and Oncology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Wang J F: "Analysis of downstream effectors of p53 on cell growth arrest and apoptosis induced by a temperature sensitive Vall38 mutant" J.Med.Dent.Sciences. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Munirajan A K,Tsutsumi-ishii Y,Mohanprasad B K,Hirano Y,Munakata N,Shanmugam G & Tsuchida N.: "p53 gene mutations in oral carcinomas from India." Int.J.Cancer. 66. 297-300 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takada S,Kaneniwa N,Tsuchida N & Koike K.: "Hepatitis B virus X gene expression is activated by X protein but repressed by p53 tumor suppresor gene product in the transient expression system." Virology. 216. 80-89 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Komiyama T,Matsumura K & Tsuchida N.: "Comparison between DNA copy number in original oral squamous cell carcinomas and their corresponding cel lines by comparative genomic hybridization." Jpn.J.Cancer Res.(in press.).

    • Related Report
      1996 Annual Research Report
  • [Publications] Koizumi,Y.,Tanaka,S.,Mou R.,Koganei,H.,Kokawa,A.,Kitamura,R.,Yamauchi,H.,Ookubo,K.,Saito,T.,Tominaga,S.,Matsumura,K.,Shimada,H.,Tsuchida,N. and Sekihara,H.: "Changes in DNA copy number in primary gastric carcinomas by comparative genomic hybridization." Clinical Cancer Res.(in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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