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Analysis of Master Genes Associated with Invasion and Metastasis by Malignant Melanoma

Research Project

Project/Area Number 13470377
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionHokkaido University

Principal Investigator

YAMAMOTO Yuhei (2003)  Hokkaido Univ., Grad. School of Medicine., Asso.Prof., 大学院・医学研究科, 助教授 (70271674)

井川 浩晴 (2001-2002)  北海道大学, 大学院・医学研究科, 助教授 (10232159)

Co-Investigator(Kenkyū-buntansha) MORIUCHI Tetsuya holkaido univ.  Hokkaido Univ., Institute for Genetic Medicine., Prof., 遺伝子病制御研究所, 教授 (20174394)
HAMADA Jun-ichi  Hokkaido Univ., Institute for Genetic Medicine., Asso.Prof., 遺伝子病制御研究所, 助教授 (50192703)
SUGIHARA Tsuneki  Hokkaido Univ., Hospital, Prof., 教授 (20002157)
山本 有平  北海道大学, 医学部附属病院, 講師 (70271674)
大久保 佳子  北海道大学, 医学部・附属病院, 医員
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥8,100,000 (Direct Cost: ¥8,100,000)
Keywordsmalignant melanoma / homeobox genes / antisense / invasion / flow cytometry / cDNA microarray
Research Abstract

Homeobox genes regulate sets of genes that determine cellular fates in embryonic morphogenesis and maintenance of adult tissue architecture by regulating cellular motility and cell-cell interactions. Our previous studies showed that a specific member, HOXD3, when overexpressed, enhanced cell motility and invasiveness of human lung cancer A549 cells (Hamada et al. Int. J. Cancer 2001; 93: 516-25 [19]). In the present study, we investigated the roles of HOXD3 in motile and invasive behavior of human malignant melanoma cells. Of seven melanoma cell lines examined here, six cell lines expressed the HOXD3 gene, whereas normal melanocytes did not. We transduced the HOXD3-antisense gene expression vector into two cell lines (A375M and MMIV). The cell transduced with the HOXD3-antisense gene showed reduced in vitro invasion of Matrigel. The transduction of the HOXD3-antisense gene also decreased cell spreading, haptotactic activity to vitronectin and laminin-1, and phagokinetic activity. To find the difference of gene expression between the HOXD3-antisense-transduced A375M cells and the control A375MNeo2 cells, we carried out cDNA microarray analysis. The results of the microarray analysis indicated that the increased expression of cdc42-interacting protein 4, KIAA0554 and tropomyosin 1, which are all associated with the cytoskeletal system, may be involved in the reduction of motile and invasive activity by the HOXD3-antisense gene transduction.
We hypothesized that HOX genes give the cells spatial information to maintain tissue-or organ-specificity in adult body and that the deregulated expression of HOX genes results in tumor development. To better understand the roles of HOX genes in melanoma genesis and subsequent malignant progression, we compared the HOX gene expression patterns among melanomas in different body sites.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] Okubo Yoshiko: "Transduction of HOXD3-antisense into human melanoma cells results in decreased invasive and motile activities."Clinical & experimental metastasis. 19(6). 503-511 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiko Okubo, Jun-ichi Hamada, Yoko Takahashi, Mitsuhiro Tada, Arata Tsutsumida, Keiji Furuuchi, Tetsuya Aoyama, Tsuneki Sugihara, Tetsuya Moriuchi: "Transduction of HOXD3-antisense into human melanoma cell results in decreased invasive and activities."Clinical & Experimental Metastasi. 19. 503-511 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 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細胞のinvitro浸潤性の低下"北海道医学雑誌. 76巻4号. 239-250 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okubo Yoshiko: "Transduction of HOXD3-antisense into human melanoma cells results in decreased invasive and motile activities"Clinical & experimental metastasis. 19(6). 503-511 (2002)

    • Related Report
      2002 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細胞の in vitro 浸潤性の低下"Skin Cancer. 76巻4号. 239-250 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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