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ヒトパピロ-ウィルスによる発がん機構の研究

Research Project

Project/Area Number 06280125
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

石橋 正英  愛知県がんセンター, ウィルス部, 部長 (70029776)

Co-Investigator(Kenkyū-buntansha) 瀬川 薫  慶応大, 医・微生物, 講師 (30114523)
神田 忠仁  国立予研, 遺伝子解析, 室長 (60134615)
清水 文七  千葉大, 医・微物第1, 教授 (10072894)
安本 茂  神奈川県がんセンター臨床研, 分子生物, 室長 (00112342)
藤永 恵 (藤永 けい / 藤永 惠)  札幌医科大, がん研・分子生物, 教授 (10045338)
松倉 俊彦  国立予防衛生研究所, ウイルス第2, 主任研究官 (70100097)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥110,500,000 (Direct Cost: ¥110,500,000)
Fiscal Year 1996: ¥36,000,000 (Direct Cost: ¥36,000,000)
Fiscal Year 1995: ¥37,000,000 (Direct Cost: ¥37,000,000)
Fiscal Year 1994: ¥37,500,000 (Direct Cost: ¥37,500,000)
Keywords子宮 / がん / パピローマウィルス / E6 / がん抑制 / APC / DLG / トランスフォーメーション / ヒト / パピローマウイルス / cDNA / 蛋白 / 接触阻止 / p53 / ヒトパピローマウイルス / E6蛋白 / E7蛋白 / two hybrid法 / リボザイム / 単鎖抗体
Research Abstract

1,子宮頚がん関連のHPV(human papillomavirus)群のE6蛋白のC末端には、がん抑制蛋白である大腸がん関連のAPC(Adenomatous polyposis coli)蛋白のC末端と酷似のアミノ酸配列モチーフが存在するのを見つけた。この配列は他のHPV群のE6には存在しない。そして、このC末端を介して、別のがん抑制蛋白であるhDLG(DLGのヒトホモローグ)などのPDZ領域と結合しており、E6によるψ2細胞の造腫瘍性トランスフォーメションにもこのC末端の結合活性が必要であることを解明した。これらの結果は、子宮頸がんの発生の機構の一部はAPCを介して起こる大腸がんの発生の機構と類似している可能性を示唆した。2,子宮頸がん由来のSiHa細胞内のE7遺伝子をtargeting vectorを用いて除去すると、細胞は殆ど増殖できなくなることを観察した。3,p53のC末端部に既知、未知の2種類の蛋白が結合でき、同末端部の生化学的活性を制御できることを見つけた。

Report

(3 results)
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Adachi,A.: "Detection of human papillomavirus type 47 DNA in malignant lesionsof epidermodysplasia verruciformis with protocols for precise typing of related HPV DNAs." J.Clin.Microbiol.34. 367-375 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Adachi,A.: "Serial transplantation in SCID mice of an epidermodysplasia verruciformis-associated squamous cell carcinoma without alteration of its histologial and virologial features." Virology. 217. 380-383 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Funaoka,K.: "High-risk HPV-positive Human Cancer Cell Lines Show Different Sensitivity to Cisplatin-induced Apoptosis Correlated with the p21wafl/Cipl Level." Cancer lett. 108. 15-23 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kinoshita,T.: "Transactivation of prothymosin-α and c-myc promoters by human papillomavirus type 16 E6 protein." Virology. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Sasagawa,T.: "Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical canser in Japan." Jpn.J.Cancer Res.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Kamakura,M.: "The 273rd codon mutants of p53 show growth modulation activities not correlated with p53-specific transactivation activity." Oncogene. 12. 2361-2367 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujita, M: "hCDC47, a human member of the MCM family : dissociation of the nucleus-bound form during S phase." J. Biol. Chem.(印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] Adachi, A.: "Evidence for propagation of human papillomavirus type 47 DNA in cells of carcinomas of epidermodysplasia verruciformis and those transplanted to SCID mice. papillomavirus of cutaneous origin." Virology. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] Adachi, A.: "Detection of human papillomavirus type 47 DNA in malignant lesions of epidermodysplasia verruciformis with protocols for precise typing of related HPV DNAs." J. Clin. Microbiol.(印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujita, M: "Inhibition of S phase entry of human fibroblasts by an antisense oligomer against hCDC47." Biochem. Biophys. Res. Commun.(印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] Shidoh, M.: "Detection of human papillomavirus DNA sequences in oral squamous cell carcinomas and their relationship to p53 and PCNA expression." Cancer. 76. 1513-1521 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Nishida: "Transcriptional repression of smooth-muscle a-actin gene associated with human papillomavirus type 16 E7 expression." Mol. Carcinogenesis. 13. 157-165 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Akutsu, N.: "p53-dependent and-independent trans-activation by the E6 protein of human papillomavirus type 16." J. Gen. Virology. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] Suzuki, T.: "Deletion in the L1 open reading frame of human papillomavirus type 6a genomes associated with recurrent laryngeal papilloma." J. Med. Virol.47. 191-197 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kanda, T.: "Occurrence of the antibody against Human Papillomavirus Type 16 Virion Protein L2 in Patients with Cervical Cancer and Dysplasia." Intervirology. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakagawa, S.: "Mutational Analysis of Human Papillomavirus Type 16 E6 Protein : Transformation Function for Human Cells and Degradation of p53 In Vitro." Virology. 212. 535-542 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsukura, T.: "Identification of genital human papillomaviruses in cervical biopsy specimens : Segregation of specific virus types in specific clinicopathologic lesions." Intern. J. Cancer. 61. 13-22 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Higashi, H: "Differences in substrate specificity between CDK2-Cyclin A and CDK2-Cyclim E in vitro." Biochem. Biophys. Res. Commun.216. 520-525 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kiyono,T.: "Inhibition of p53-mediated transactivation by E6 of type 1,but not type 5,8,or 47 human papillomavirus of cutaneous origin." J.Virol.68. 4656-4661 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Inoue,T.: "Correlation between tumorigenicity and expression levels or splicing patterns of transcripts of human papillomavirus type 16 E6 gene." Jpn.J.Cancer Res.85. 357-363 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fujinaga,Y.: "Sequence variation of human papillomavirus type 16 E7 in preinvasive and invasive cervical neoplasias." Virus Genes. 9. 85-92 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shirasawa,H.: "Transcription-modulatory activity of full-length E6 and E6^*I proteins of human papillomavirus type 16." Virology. 203. 36-42 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shimizu,K.: "Alternative splicing of human papillomavirus type-16 E6-mRNA in mouse and monkey cell lines." Int.J.Oncol.4. 971-976 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Honda,A.: "Human papillomavirus type60-associated plantar wart-ridged wart-." Arch.Dermatol.130. 1413-1417 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsukura,T.: "Identification of genital human papillomaviruses in cervical biopsy specimens:Segregation of specific virustypes in specific clinicopathologic lesions." Intern.J.Cancer. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kanda,T.: "Wild type p53 transactivates both transcription and DNA replication through the DNA binding site." Mol.Cell.Biol.14. 2651-2663 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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