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Analysis of oncogenes and tumor-suppressor genes in oral cancers and the application to diagnosis

Research Project

Project/Area Number 01440075
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Morphological basic dentistry
Research InstitutionFaculaty of Dentistry, Tokyo Medical & Dental University

Principal Investigator

TSUCHIDA Nobuo  Oral Microbiology, Prof., 歯学部, 教授 (60089951)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Nobuyoshi  Oral Microbiology, Res. Asso., 歯学部, 助手 (90014258)
IKEDA Masaaki  Oral Microbiology, Res. Asso., 歯学部, 助手 (20193211)
ICHO Tateo  Oral Microbiology, Res. Asso., 歯学部, 助手 (80213015)
YAMAMOTO Hajime  Oral Pathology, Prof., 歯学部, 教授 (60005014)
ENOMOTO Shoji  2nd Dept. Oral Surgery, Prof., 歯学部, 教授 (40013940)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥35,900,000 (Direct Cost: ¥35,900,000)
Fiscal Year 1991: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1990: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1989: ¥28,700,000 (Direct Cost: ¥28,700,000)
KeywordsSquamous Cell Carcinoma / Oncogene / Tumor Suppressor Gene / Ras Gene / p53 Gene / PCR (polymerase chain reaction) / SSCP (single strand confomation polymorphysm) / p53 / ras / PCR / 病理切片 / SSCP / 口腔癌 / 口腔扁平上皮癌 / Polymerase Chain Reaction(PCR) / 骨肉腫 / 癌抑性遺伝子 / Polymerase chain Reaction(PeR)
Research Abstract

Human cancers emerge from a normal cell after multiple genetic changes of protooncogenes and tumor suppressor genes by multistep process. In the present research we focused on squamous cell carcinomas (SCC) in the oral cavity and examined abnormalities of ras and erbB1 (EGFR) protooncogenes, and p53 tumor suppressor gene.
ras mutation : 29 tumor lesions of oral SCC were examined for the activational mutations of codons 12, 13, and 61 of N-, H- K-ras genes. Mutations were detected by hybridization of PCR (polymerase chain reaction)-amplified DNA with allele specific oligonucleotide probes or by PCR-SSCP (single strand conformation polymorphysm) analysis. As a result we could not detect mutation except for two cell lines which had mutations of codons 12 (HOC313) and 13 (ZA) of H-ras. Analysis of parafin-embedded sections showed that the tumor sample of HOC313 had the mutation at the time of initial diagnosis. Although the mutation of ZA was detected in the tumor tissue used for the cell l … More ine establishment, the normal epithelium and leukoplakia lesion were negative. From these results frequency of ras mutation in oral SCC is considerablly low compared with those of adenomas, thus suggesting that ras mutation may not important in tumorigenesis of oral SCC.
p53 gene mutation : 15 oral SCC cell lines were examined for the presence of the mutation by cDNA-SSCP and exon-SSCP anlaysis, followed by direct sequencing. As a result, p53 gene mutations were found in 14 cell lines and were localized from cadon 126 to cadon 305. Two mutational hot-spots were found in codon 248 (3 cases) and the spliincg donor sequence of exon 6 (2 cases). Thirteen out of 14 mutations were point mutations including 10 missense mutations.
Analysis of EGFR : increased capacity for EGF binding was observed in all the examined 4 cases of oral SCC.
From these results it is anticipated that p53 gone mutations and increased capacity for EGF binding play important roles in the genesis of oral SCC, thus suggesting that both will be good diagnostic markers for SCC. Less

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Tadokoro,K.,Ueda,M.,Oshima,T.,Fujita,K.,Rikimaru,K.,Takahashi,N.,Enomoto,S.,and Tsuchida,N.: "Activation of oncogenes in human oral cancer cells; a novel codon 13 mutation of c-H-ras-1 and concurrent amplifications of c-erbB-1 and c-myc." Oncogene. 4. 499-505 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] E.Sakai,and N.Tsuchida: "Most human squamous cell carcinomas in the oral cavity contain mutated p53 tumor suppressor genes." Oncogene. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] R.Rikimaru,K.Tadokoro,T.Yamamoto,S.Enomoto,and N.Tsuchida: "Gene amplidication and overexpression of epidermal growth factor receptor in squamous cell carcinoma of heads and neck cancer." Head & Neck. 14. 8-13 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 大島 朋子: "ヒト骨肉腫細胞における癌抑制遺伝子の関与" 口腔病学会雑誌. 58(1). 310-328 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 上田 晶義: "口腔腫瘍における癌遺伝子の解析" 日本口腔外科学会雑誌. 36. 2211-2225 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] E.Hara,T.Ohshima,T.Ishii,W.Sugino,K.Tsutsui,S.Nakada,N.Tsuchida,and K.oda: "Mechanism of induction of ceilular DNA synthesis by the adenovirus EIA 12S cDNA product." Exp.Cell Res.,. ((1992))

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tadokoro, K., Ueda, M., Oshima, T., Fujita, K., Rikimaru, K., Takahashi, N., Enomoto, S., and Tsuchida, N.: "Activation of oncogenes in human oral cancer cells ; a novel codon 13 mutation of c-H-ras-1 and concurrent amplifications of c-erbB-1 and c-myc." Oncogene. 4. 499-505 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Rikimaru, K., Tadokoro, K., Yamamoto, T., Enomoto, S., and Tsuchida, N.: "Gene amplification and overexpression of epidermal growth growth factor receptor in squamous cell carcinoma of head and neck cancer." Head & Neck. 4. 8-13 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sakai, E. and Tsuchida, N.: "Most human squamous cell carcinomas in the oral cavity contain mutated p53 tumor suppressor genes." Oncogene.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Oshima, T.: "Roles of tumor suppressor genes in human osteosarcoma cells." J. Stomatol. Soc. Jpn.58. 111-129 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ueda, M.: "Studies on oncogenes in human oral tumors" Jpn. J. Oral Maxillofac. Surg.36. 2211-2225 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hara, H., Ohshima, T., Ishii, W., Sugino, K., Tsutsui, S., Nakada, N., Tsuchida, N., and Oda, K.: "Mechanism of induction of cellular DNA synthesis by the adenovirus E1A 12S cDNA product" Exp. Cell. Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] E.Sakai,and N.Tsuchida: "Most human squamous cell carcinomas in the oral cavity contain mutated p53 tumor suppressor genes." Oncogene. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] R.Rikimaru,K.Tadokoro,T.Yamamoto,S.Enomoto,and N.Tsuchida: "Gene amplidication and overexpression of epidermal growth factor receptor in squamous cell carcinoma of head and neck cancer." Head & Neck. 14. 8-13 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 大島 朋子: "ヒト骨肉種細胞における癌抑制遺伝子の関与" 口腔病学会雑誌. 58(1). 310-328 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] E.Hara,T.Ohshima,T.Ishii W.Sugino,K.Tsutsui,S.Nakada,N.Tsuchida,and K.Oda: "Mechanism of induction of cellular DNA synthesis by the adenovirus E1A 12S cDNa product." Exp.Cell Res.,.

    • Related Report
      1991 Annual Research Report
  • [Publications] 上田 晶義: "口腔腫瘍における癌遺伝子の解析 Studies an oncogenes in human oral tumors" 日本口腔外科学会雑誌. 36. 2211-2225 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 石井 菜穂子,酒井 英紀,山本 肇,榎本 昭二,土田 信夫: "PCR法を用いたヒト口腔扁平上皮癌の病理切片におけるHー<ras>___ー codons12,13の活性化の検索" 歯科基礎医学会雑誌. 32(補). 155 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] E.Sakai,N.Ishii,S.Enomoto,H.Yamamoto and N.Tsuchida: "Frequency of <ras>___ー gene activation in oral tumor lesions." 歯科基礎医学会雑誌. 32(補). 156 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 大島 朋子,池田 正明,土田 信夫: "ヒト骨肉腫およびヒト口腔癌細胞における癌抑制遺伝子産物の解析" 歯科基礎医学会雑誌. 32(補). 156 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 大島 朋子: "ヒト骨肉腫細胞における癌抑制遺伝子の関与" 口腔病学会雑誌. 58/1. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Eiki Sakai,Naoko Ishii and Nobuo Tsuchida: "Infrequent <ras>___ー gene aetivotion in Japanese oral squomous Cell Carcinoma"

    • Related Report
      1990 Annual Research Report
  • [Publications] Koichi Rikimaru,Keiko Tadokoro,Tadashi Yamamoto,Shoji Enomoto and Nobuo Tsuchida: "Gene amplification and overexpression of epidermal growth factor reeeptor in Squamous cell careinoma of head and neck cancer"

    • Related Report
      1990 Annual Research Report
  • [Publications] Tadokoro,K.,Ueda,M.,Ohshima,T.,Fujita,K.,Rikimaru,K.,Takahashi,N.,Enomoto,S.,and Tsuchida,N.: "Activation of onecogenes in human oral cancer cells:a novel codon 13 mutation of cーHーrasー1 and concurnent amplifieations of cーerbBー1 and cーmyc" Oncogene. 4. 499-505 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 大島朋子・土田信夫: "ヒト骨肉腫における癌抑制遺伝子の解析" 歯科基礎医学会雑誌. 31ーS. 22 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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