2003 Fiscal Year Final Research Report Summary
Analysis of Master Genes Associated with Invasion and Metastasis by Malignant Melanoma
| Project/Area Number |
13470377
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Plastic surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
YAMAMOTO Yuhei Hokkaido Univ., Grad. School of Medicine., Asso.Prof., 大学院・医学研究科, 助教授 (70271674)
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| 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)
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| Project Period (FY) |
2001 – 2003
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| Keywords | malignant melanoma / homeobox genes / antisense / invasion / flow cytometry / cDNA microarray |
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| 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.
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Research Products
(2 results)
