2000 Fiscal Year Final Research Report Summary
Heterotopic expression of morphogenetic genes and invasiveness in human melanoma cells
| Project/Area Number |
11671779
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
IGAWA Hiroharu Hokkaido Univ.Hospital, assistant professor, 医学部・附属病院, 講師 (10232159)
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| 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)
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| Project Period (FY) |
1999 – 2000
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| Keywords | homeobox gene / HOXD3 / melanoma / metastatic activity / invasive activity / motility |
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| 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.
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