| Project/Area Number |
10670955
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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 |
Hematology
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| Research Institution | NAGASAKI UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
JINNAI Itsuro Nagasaki University School of Medicine, Lecturer, 医学部・附属病院, 講師 (70162823)
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| Co-Investigator(Kenkyū-buntansha) |
TUKASAKI Kunihiro Nagasaki University School of Medicine, Assistant, 医学部, 助手 (40274659)
TOMANAGA Masao Nagasaki University School of Medicine, Professor, 医学部, 教授 (40100854)
長井 一浩 長崎大学, 医学部・附属病院, 助手 (30304942)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | ATL / stromal cells / long-term coculture sytem / cobblestone area / adhesion molecule / signal transduction / cobble stone area / cobblestone area |
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| Research Abstract |
(1) Proliferation of ATL cells in coculture system with MS-5 cell line
We developed a coculture system involving ATL cells and murine marrow stromal cells, MS-5. ATL cells of several cell lines established from ATL patients were used. The ATL cells grew in close contact with stromal layer of MS-5 and formed so-called cobblestone areas (CA). ATL cells of a IL-2 dependent cell line also showed a similar growth pattern without addition of IL-2 in this coculture system. The mechanism of this proliferation appears to be related with the signal transduction system through some adhesion molecules.
(2) Analyses of the production of HTLV- 1 related proteins
We analyzed the production of HTLV-1 related proteins of the ATL cells forming CAs on MS-5 layers using an immunocytochemical-stain method. The production of tax and gag proteins of ATL cells decreased or vanished by coculturing on MS-5 layers. Study on expression of mRNA of tax gene and other genes those trans-activated by tax protein using in situ hybridization method is ongoing. This coculture method showed the proliferation of ATL cells without production of HTLV-1 related protein, suggesting to be useful for analysis of the clinical pathophysiology of ATL.
(3) Phosphorylation of JAK/STAT proteins of ATL cell
We compared tyrosine phosphorylation pattern of JAK/STAT protein between the ATL cells cocultured on MS-5 layers and those cultured without MS-5 cells. Some ATL cell line demonstrated that tyrosine phosphorylation status of STAT3 was down-regulated by coculturing on MS-5. It appears that abnormalities of the signal transduction system through adhesion molecules reflect the clinical pathophysiology of ATL patients.
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