2003 Fiscal Year Final Research Report Summary
Study of transforming growth factor β in melanocyte proliferation and differentiation of mouse neural crest cells via stem cell factor/KIT signaling
| Project/Area Number |
14570828
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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 |
Dermatology
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
KAWAKAMI Takahiro St.Marianna University School of Medicine, Department of Dermatology, Lecturer, 医学部, 講師 (20297659)
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| Project Period (FY) |
2002 – 2003
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| Keywords | TGF β / neural crest cells / melanocyte / mouse NCC / malignant melanoma / differentiation / SCF / KIT / proliferation |
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| Research Abstract |
SCF is essential to the migration and differentiation of melanocytes during embryogenesis based on the observation that mutations in either the SCF gene, or its ligand, KIT, result in defects in coat pigmentation in mice. TGF β1 has been implicated in the regulation of both cellular proliferation and differentiation. NCC-melb4, an immortal cloned cell line, was cloned from a mouse NCC. NCC-melb4 cells provide model to study the specific stage of differentiation and proliferation of melanocytes. They also express KIT as a melanoblast marker. Using the NCC-melb4 cell line, we investigated the effect of TGF β1 on the differentiation and proliferation of immature melanocyte precursors. Immunohistochemically, NCC-melb4 cells showed TGF β1 expression. The anti-TGF β1 antibody inhibited the cell growth, and downregulated the KIT protein and mRNA expression. To further investigate the activation of autocrine TGF β1, NCC-melb4 cells were incubated on-exogenous TGF β1 culture medium. KIT protein decreased with anti-TGF β1 antibody concentration in a dose-dependent fashion. We concluded that in NCC-melb4 cells, TGF β1 promotes melanocyte precursor proliferation in autocrine and/or paracrine regulation. We further investigated the influence of TGF β1 in vitro using a NCC primary culture system from wild-type mice. Anti-TGF β1 antibody decreased the number of KIT positive NCC. I addition, the anti-TGF β1 antibody supplied within the wild-type neural crest explants abolished the growth of NCC. These results indicate that TGF β1 affect melanocyte precursor proliferation and differentiation in the presence of SCF/KIT in an autocrine/paracrine manner.
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Research Products
(11 results)
