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染色体導入による転移抑制遺伝子の同定

Research Project

Project/Area Number 06281244
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionTottori University

Principal Investigator

押村 光雄  鳥取大学, 医学部, 教授 (20111619)

Co-Investigator(Kenkyū-buntansha) 久郷 裕之  鳥取大学, 医学部, 助手 (40225131)
清水 素行  鳥取大学, 医学部, 助教授 (80130756)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥25,400,000 (Direct Cost: ¥25,400,000)
Fiscal Year 1996: ¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 1995: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1994: ¥7,300,000 (Direct Cost: ¥7,300,000)
Keywordsがん転移 / 転移抑制遺伝子 / 微小核細胞融合 / 染色体導入 / マウスメラノーマ細胞 / 微小核融合法 / ヒト18番染色体 / 微小核細胞融合法
Research Abstract

我々は、未知の転移抑制に関わる遺伝子のマッピングとクローニングを行うために、Y染色体を除く全ての正常細胞由来の染色体を微小核細胞融合法を用いて、マウスメラノーマ高転移株(B16-F10)へ移入し、ヌードマウスにおける造腫瘍性およびin vitro増殖特性の変化に対して抑制効果を示さないマイクロセルハイブリッド(MH)クローン(3番、4番、6番、8番、12番、13番、18番、X染色体)を選別した。分離した23種類の異なったヒト染色体移入クローン、計230クローンは、染色体解析により移入染色体の確認を行った。完全な移入染色体が高率に認められたMHクローンを用いて、転移抑制染色体を同定するための一次スクリーニングとして、ヌードマウスにおける造腫瘍性およびin vitro増殖特性についての検索を行い、これらのがん形質に対して抑制効果を示さない染色体移入クローン(3番、4番、6番、8番、12番、13番、18番、X染色体)を選別した。さらに、これらの染色体移入クローンは、以下の2種類の方法により転移能を検索した。さらに、選別した染色体移入クローンの転移能の抑制効果を受精鶏卵への注入による胎児肝転移を指標にした受精鶏卵法およびマウスへの静脈内注入による肺転移を指標にした手法により検索した。受精鶏卵法は、受精鶏卵漿尿膜上の血管へ5×10^5個の細胞を移植後、embryoの肝臓への転移結節を観察する。親細胞においては肝臓への平均転移結節数が74.6個で、その他の臓器(心臓、胃など)にも多数の転移結節が認められた。一方、18番染色体移入クローン(#18-1,9)においては、肝臓および他臓器に対して著しい転移結節数の減少が認められ、平均転移結節数は3.1および7.9であり、統計的に有意差が認められた(P<0.05)。他の3番、4番、6番、8番、12番、13番、X染色体移入クローンにおいては、親細胞と同様に高い転移能を示した。これらのことより、18番染色体上に転移抑制に係わる遺伝子の存在が示唆された。一方、マウスへの静脈内注入による肺転移を指標にした手法においては、3番、8番染色体移入クローンに、顕著な転移形成の低下が認められた。
以上の結果から、(1)3番、8番染色体上にも転移抑制遺伝子が存在し、(2)受精鶏卵法での結果との相関を示さなかったことより、異なる転移能検索法を用いることが、複数の転移抑制遺伝子の検索に有効であることが示唆された。

Report

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

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Tanaka,K.,Kikuchi-Yanoshita,R.,Muraoka,M.,et al.: "Suppression of tumorigenicity and invasiveness of colon carcinoma cells by introduction of normal chromosome 8p12-pter." Oncogene. 12. 405-410 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ichikawa,T.,Nihei,N.,Kuramochi H.,et al.: "Metastasis suppressor genes for prostate cancer." The Prostate Suppl.6. 31-35 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nihei,N.,Ichikawa,T.,Kawana,Y.,et al.: "Mapping of metastasis suppressor gene(s)for rat prostate cancer on the short arm of human chromosome 8 by irradiated microcell-mediated chromosome transfer." Genes,Chrom.& Cancer. 17. 260-268 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oshimura,M.and Barrett,J.C.: "Multiple pathways to cellular senescence:Role of telomerase repressors." Euro.J.Cancer. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Ichikawa,T.: "Suppression of metastasis of rat prostatic cancer by introducing human chromosome 8." Cancer Res.54. 2299-2302 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujiwara,Y.: "A3-Mb physical map of the chromosome region 8q21.3-p22,including a 600-kb region commonly deleted in human hepatocellular carcinoma,colorectal cancer,and non-small cell lung cancer." Gene,Chr.,and Cancer. 10. 7-14 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Parshad,R.: "Complementation of a DNA repair deficiency in six human tumor cell lines by chromosome 11." Hum.Genet.88. 524-528 (1992)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ichikawa,T.: "Localization of metastasis suppressor gene(s)for prostatic cancer to the short arm of human chromosome 11." Cancer Res.52. 3486-3490 (1992)

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyamoto,S.: "Increased actin cable organization after single chromosome introduction:association with suppression of in vitro cell growth rather than tumorigenic suppression." Mol.Carcinogen.10. 88-96 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshida,M.A.: "In vitro growth suppression and morphological change in a human renal cell carcinoma cell line by the introduction of normal choromosome 3 viamicrocell-fusion." Mol.Carcinogen.9. 114-121 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Satoh,H.: "Suppression of tumorigenicity of A549 lung adenocarcinoma cells by human chromosomes 3 and 11 introduced via microcell-mediated chromosome transfer." Mol.Carcinogen.7. 157-164 (1993)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kohno,T.: "Deletion mapping of chromosome 3p in human uterine cervical cancer." Oncogene.8. 1825-1832 (1993)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,K.: "Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region." Oncogene.8. 2253-2258 (1993)

    • Related Report
      1996 Annual Research Report
  • [Publications] Loh,W.E.Jr.: "Human chromosme 11 contains two different growth suppressor genes for embryonal rhabdomyosarcoma." Proc.Natl.Acad.Sci.USA. 89. 1755-1759 (1992)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nihei,N.et al.: "Mapping of metastasis suppressor qene (s) for rat prostatic cancer on human chromosome 8 by irradiation microcell-mediated chromosome" Genes,Chromosomes and Cancer. in press.

    • Related Report
      1995 Annual Research Report
  • [Publications] Uzawa,N.et al.: "Suppression of tumoriqenicity in three different celllines of human oral squamous cell carcinoma by introduction of chromosome 3p via microcell-mediated chromosome transfer" Onoogene. 11. 1997-2004 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nihei,N.et al.: "Localization of metastasis suppressor gene (s) for rat prostatic cancer to the long arm of human chromosome 10" Genes,Chromosomes and Cancer. 14. 112-119 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Horikawa,I.et al.: "Forced expression of YL-1 protein suppresses the anchorage-independent growth of kirsten sarcoma virus-trans formed NIH3T3 cells" Exp.Cell Res.220. 17 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Uejima,H.et al.: "A normal human chromosome 2 induces cellular senescence in the human cervical carcinoma cellline,SiHa" Genes,Chromosomes and Cancar. 14. 120-127 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ohmura,H.et al.: "Restoration of cellular senescence program and repression of telomerase by human chromosome 3" Jpn.J.Cancer Res.86. 899-904 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kurimasa,A.et al.: "Construction of 110 cosmid markers and a 4.5 Mb YAC contig on human chromosome 8p12-q11" Genomics. 28. 147-153 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Horikawa,I et al.: "A normal human chromosome 3 suppresses tumoriginicity of human cervical carcinoma cell line,SiHa" Chromosome Information Service. 58. 4 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kugoh,H.et al.: "Isolation and mapping of 186 new DNA markers on human chromosome 1" Genomics. 27. 207-210 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Horikawa,I.et al.: "Subchromosomal mapping of a putative transformation suppressor gene on human chromosome 1" Jpn.J.Cancer Res.86. 444-450 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Zenklusen,J.C.et al.: "Human chromosome 11 inhibits tumorigenicity of a murine squamous cell carcinoma cellline" Genes,Chromosomes and Cancer. 13. 47-53 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamada,H. et al.: "Suppression of endometrial carcinoma cell tumorigenicity by human chromosome 18" Genes,Chromosomes and Cancer. 13. 18-24 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Horikawa,I.et al.: "Frame-shift mutation and reduced transcript of p53 gene in a renal cell carcinoma cell line,RCC23" Hum.Mol.Genet.4. 771-773 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Horikawa,I.et al.: "Molecular cloning of a novel human cDNA on chromosome 1q21 and its mouse homolog encoding a nuclear protein with DNA-binding ability" Biochem.Biophys.Res.Commun.208. 999-1007 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Horikawa,I.et al.: "An amino-terminally truncated p53 protein expressed in a human choriocarcinoma cell line, CC1" Hum.Mol.Genet.4. 313-314 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ogata,T.et al.: "Genetic complementation of the immortal phenotype in group D cell lines by introduction of chromosome 7" Jpn.J.,Cancer Res.86. 35-40 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sasaki,M.et al.: "Evidence for multiple pathways to cellular senescence" Cancer Res.54. 6090-6093 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ichikawa,T.et al.: "Suppression of metastasis of rat prostatic cancer by introducing human chromosome 8" Cancer Res.54. 2299-2302 (1994)

    • Related Report
      1995 Annual Research Report

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

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