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Heterotopic expression of morphogenetic genes and invasiveness in human melanoma cells

Research Project

Project/Area Number 11671779
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

IGAWA Hiroharu  Hokkaido Univ.Hospital, assistant professor, 医学部・附属病院, 講師 (10232159)

Co-Investigator(Kenkyū-buntansha) MORIUCHI Tetsuya  Hokkaido Univ.Inst.Genetic Medicine, chief professor, 遺伝子病制御研究所, 教授 (20174394)
HAMADA Junichi  Hokkaido Univ.Inst.Genetic Medicine, associate professor, 遺伝子病制御研究所, 助教授 (50192703)
SUGIHARA Tsuneki  Hokkaido Univ.Grad.School of Med., chief proffesor, 大学院・医学研究科, 教授 (20002157)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordshomeobox gene / HOXD3 / melanoma / metastatic activity / invasive activity / motility / HOX D3
Research Abstract

Since homeobox-containing genes (HOX genes) are a family of transcriptional regulators, which give cells positional information in morphogenesis, cancer metastasis can be explained as a heterotopic expression of HOX genes. In our previous study, we transfected HOXD3 gene into human lung cancer A549 cells and studied alterations in adhesiveness, migration and invasiveness of the tumor cells.
HOXD3 gene was expressed in almost all of the human melanoma cell lines, but normal melanocyte had no HOXD3 expression. So we constructed a mammalian expression vector containing HOXD3 gene in the antisense orientation and transfected it into A375M, which is a melanoma cell line and investigated the invasive activity and motility.
In the present study, the HOXD3-antisense transfectants showed decreased invasive activity through Matrigel and decreased migratory activities toward vitronectin and laminin-1 compared to their parent cells and control neo-transfectants.
HOXD3-antisense expression decreased the invasive activity and motility. HOXD3-antisense transfectants showed increased expression of cytoskelton-related genes and did not show spreading on Matrigel and laminin-1.
These findings suggest that expression of HOXD3 may cause changes in the expression of cytoskelton-related genes and thereby may be responsible for the increased invasiveness and metastatic property seen in melanoma cells.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] 大久保佳子: "ヒト悪性黒色腫におけるホメオボックス遺伝子と細胞接着分子の発現"Skin Cancer. 14巻3号. 299-301 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 大久保佳子: "ホメオボックス遺伝子HOXD3アンチセンス発現ベクター導入によるヒト悪性黒色腫のin vitro浸潤性の低下"北海道医学雑誌. (7月掲載予定). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okubo Y: "HOXD3 and integrin β3 in malignant melanoma cells."Skin Cancer. 14 (3). 299-301 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okubo Y: "Overexpression of the Human HOXD3-antisense in Melanoma Cells Results in Decreased Invasive Activity."Hokkaido J Med.Sci.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 大久保佳子: "ヒト悪性黒色腫におけるホメオボックス遺伝子と細胞接着分子の発現"Skin Cancer. 14 卷3号. 299-301 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大久保佳子: "ホメオボックス遺伝子HOXD3アンチセンス発現ベクター導入によるヒト悪性黒色腫のin vitro浸潤性の低下"北海道医学雑誌. (7月掲載予定). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 尾松 徳彦: "オメホボックス遺伝子の過剰発現によるヒト肺癌細胞A549の細胞運動性および浸潤性の増強"北海道医学雑誌. 74巻5号. 367-376 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大久保 佳子ほか: "ヒト悪性黒色腫におけるオメホボックス遺伝子と細胞接着分子の発見"Skin cancar. 14巻3号. 299-301 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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