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脳神経系腫瘍発生に関与する癌抑制遺伝子の機能とその異常の解析

Research Project

Project/Area Number 07273254
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKumamoto University

Principal Investigator

佐谷 秀行  熊本大学, 医学部, 教授 (80264282)

Co-Investigator(Kenkyū-buntansha) 西 徹  熊本大学, 医学部付属病院, 助手 (00264309)
荒木 令江  熊本大学, 医学部, 助手 (80253722)
Project Period (FY) 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥21,600,000 (Direct Cost: ¥21,600,000)
Fiscal Year 1997: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1995: ¥7,500,000 (Direct Cost: ¥7,500,000)
Keywords脳腫瘍 / グリオーマ / 癌抑制遺伝子 / 10番染色体 / マイクロサテライト / neuralized / NF2 / warts / PARP / dlg / APC / NF1
Research Abstract

脳神経系に発生する腫瘍は、悪性は勿論のこと、良性腫瘍でも発生部位によっては患者の生命を脅かす事が時にあり、治療の最も困難な疾病の一つと言える。本研究は脳神経系腫瘍形成の要因となる各種癌抑制遺伝子の変化と、それによって生じる生物学的特性を明らかにし、遺伝子異常と疾患の表現型との関連を明確にすることを目的とした。更に、それらの遺伝子産物が関与する細胞内シグナルについて解析を行った。
本年度の成果を要約すると:
1.グリオーマにおける10番染色体長腕の異常をマイクロサテライトマーカーを用いて解析し、GradeIII及びIVの悪性グリオーマにおいて高頻度に欠失している部位はD10S192とD10S566にはさまれる11.8cRの領域であることを見いだした。
2.上記高頻度欠失両域内にショウジョウバエ神経分化関連遺伝子neuralizedのヒト相同遺伝子が存在することを見いだし、その全長cDNAのクローニング(h-neuと命名)を行った。h-neuはヒト正常脳では発現が見られるが、悪性グリオーマ組織ならびに細胞株では発現の消失あるいは変異が認められた。
3.ショウジョウバエ腫瘍抑制遺伝子wartsの相同遺伝子(h-warts)のクローニングを行い、この遺伝子が悪性グリオーマや乳癌に置いて高頻度に欠失している6q25上のマーカーに近接して存在することを見いだした。
4.NF2遺伝子産物であるmerlinが細胞内でポリ(ADPリボース)ポリメラーゼ(PARP)ならびにKu85と結合することを見いだした。

Report

(3 results)
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Nakamura, H.et al.: "Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region." Oncogene. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makino, K.et al.: "Cloning and characterization of NE-dlg:a novel human homolog of the Drosophila discs large(dlg)trmor suppressor protein interacts with the APC protein." Oncogene. 14. 2425-2434 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koga, H.et al.: "Impairment of cell adhesion by expression the mutant neurofibromatosis type 2 (NF2)genes which miss exons in the ERM-homology domain." Oncogene. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyake, H.et al.: "Overexpression of Bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer." Oncogene. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okamoto, I.et al.: "Molecular detection of cancer cells by competitive reverse transcriptation-polymerase chain reaction analysis of specific CD44 splice variants." J.Natl.Cancer Inst.90. 307-315 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sasaki, J.et al.: "Expression of CD44 splicing in lung cancers:Dominant expression of CD44v8-10 in non-small cell lung carcinomas." Int.J.et al.12. 525-533 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makino,K.: "Cloning and characterization of NE-dig : a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein." Oncogene. (刊行予定). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Izawa,I: "Phosphorylation of neurofibromatosis type 1 gene product (neurofibromin) by cAMP-dependent protein kinase." FEBS Letters. 382. 53-59 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Xiang,H.: "Evidence for p53-Mediated Modulation of Neuronal Viability." J.Neurosci. 16. 6753-6765 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakuma,S.: "Receptor protein tyrosine kinase DDR is up-regulated by p53 protein." FEBS Letters. 398. 165-169 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahashi,R.: "Transfection of wild-type p53 induces differentiation in a human gingival carcinoma cell line in vivo." Int.J.Cancer. 32. 533-539 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishi,T.: "High-efficiency in vivo gene transfer using intra-arterial plasmid DNA injection follwing in vivo electroporation." Cancer Res.56. 1050-1055 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Izawa,I.: "Phosphorylation of neurofibromatosis type 1 gene product (neurofibromin) by cAMP-dependent protein kinase." FEBS Letters(刊行予定). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishi,T.: "High-efficiency in vivo gene transfer using intra-arterial plasmid DNA injection following in vivo electroporation." Cancer Res.(刊行予定). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inagaki,T.: "Transfection of wild-type p53 induces differentiation in a human gingival carcinoma cell line in vivo." Europ.J.Cancer(刊行予定). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tamura,T.: "Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells." Oncogene. 11. 1939-1946 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takahashi,K.: "CD44 hyaluronate binding influences growth kinetics and tumorigenicity of human colon carcinomas." Oncogene. 11. 2223-2232 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nagasaka,S.: "Alternative RNA splicing of the hyaluronic acid receptor CD44 in the normal human brain and in brain tumors." J.Neurosurg. 82. 858-863 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sakuma,S.: "Radiation induction of the receptor tyrosine kinase gene Ptk-3 in normal rat astrocytes." Radiat.Res.143. 1-7 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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