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活性型低酸素応答性転写因子HIF-1α遺伝子導入マウスの作製および解析

Research Project

Project/Area Number 14028043
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHiroshima University

Principal Investigator

谷本 圭司  広島大学, 原爆放射線医科学研究所, 助手 (90335688)

Project Period (FY) 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥3,900,000 (Direct Cost: ¥3,900,000)
Keywordshypoxia / hypoxia-inducible factor / angiogenesis / genetic polymorphism / transgenic mice / transcription factor / head and neck cancer / tumor-stroma
Research Abstract

hypoxia-inducible factor-1 (HIF-1)は低酸素刺激に応答する転写因子で,癌組織においても重要な役割を果たしていると考えられる。本申請は,ヒトで見出された遺伝子型のHIF-1α(活性型HIF-1α)を遺伝子導入したマウスを作製し,癌の増殖・進展および転移能に与える遺伝子型の影響を明らかにすることを目的とする。ヒト口腔扁平上皮癌検体を用いた解析の結果,P582SまたはA588Tのどちらかの遺伝子アリールを持つ患者(ヘテロ型)の腫瘍は,WT(ホモ型)のそれよりも有意に多くの腫瘍内血管を持つこと,さらに初診時腫瘍径が大きいことを見いだし,HIF-1α遺伝子の転写活性化能に違いが認められる遺伝子多型が腫瘍の増殖や進展に関与する可能性が示された(投稿中)。現在,CMVプロモーターを用いた,FLAG標識ヒトHIF-1α野性型(WT)またはアミノ酸置換型(P582SおよびA588T)遺伝子発現ベクター導入BALB/cマウスを作製中(genotyping)である。また,腫瘍移植実験に用いるため,FLAGのみ,FLAG HIF-1αWT,またはP582S, A588Tの計4種類の発現ベクターをMMSV-BALB/3T3細胞に安定遺伝子導入した。今後,異なる遺伝子型腫瘍の移植実験等により,腫瘍-間質間相互作用の役割等,癌の増殖・進展および転移能について検討する予定である。

Report

(1 results)
  • 2002 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Teresa Pereira: "Identification of Residues Critical for Regulation of Protein Stability and the Transactivation Function of the Hypoxia-Inducible Factor-1α by the von Hippel-Lindau Tumor Suppresor Gene Product"Journal of Biological Chemistry. 278. 6816-6823 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuko Miyazaki: "Identification of Functional Hypoxia Response Elements in Promoter Region of the DEC1 and DEC2 Gene"Journal of Biological Chemistry. 277. 47014-47121 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ken Hirao: "Targeted gene delivery to human osteosarcoma cells with magnetic liposomes under a magnetic field"International Journal of Oncology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ryo Okamoto: "O6-methylguanine-DNA methyltransferase (MGMT)as a determinant of resistance to camptothecin derivatvies"Japanese Journal of Cancer Research. 93. 93-102 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ryo Okamoto: "Unique action determinants of double acting topoisomerase inhibitor, TAS-103"International Journal of Oncology. 19. 921-927 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Keiji Tanimoto: "Human Genetics"Research Signpot, Kerala, India (editors, K.Hiyama and E.Hiyama) (in press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2018-03-28  

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