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The role of BMP and Kit in melanocyte and melanoma cell differentiation

Research Project

Project/Area Number 18591261
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionSt.Marianna University School of Medicine

Principal Investigator

KAWAKAMI Tamihiro  St.Marianna University School of Medicine, Department of Dermatology, Associate professor (20297659)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsNeural crest cells / Melanocyte / BMP / Kit / Primary culture of NCC / noggin / Melanoblast / Melanoma / 神経冠細胞 / Kitl伝達系 / 悪性黒色腫
Research Abstract

Genes encoding Kit and the Kit ligand (RI) play essential roles in the differentiation of melanoblasts. We previously established three immortal but distinct cell populations of mouse neural crest (NC) cells. NCCmelb4M5 cells do not express Kit and grow independently of KL; they have the potential to differentiate into NCCmelb4 cells, which are Kit-positive melanocyte precursors. NCCmelan5 cells show the characteristics of differentiated melanocytes. All three cell lines demonstrated BMP-receptor expression. BMP-4 upregulated Kit protein and mRNA expression in most immature NCCmelb4M5 cells. Noggin, a BMP-4 antagonist, dramatically decreased the Kit expression induced by BMP-4. Western blot analysis revealed that extrinsic BMP-4 leads to the phosphorylation of Smads in NCCmelb4M5 cells. Using transfected Kit-promoter reporter we showed BMP-4 could activate Kit promoter in transfected NCCmelb4M5 cells. We conclude that BMP-4 is active and is involved in the regulation of Kit expression on most immature melanocyte precursors. We further investigated the influence of BMP-4 in vitro using primary NC cells cultured from wild-type mice. Addition of BMP-4 to the medium increased the number of Kit-positive cells compared to diluent-treated controls. We have identified BMP-4 as an important factor for prenatal Kit-negative melanoblasts just prior to entering the Kit-dependent cycle of melanogenesis.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (28 results)

All 2008 2007 2006

All Journal Article (22 results) (of which Peer Reviewed: 10 results) Presentation (3 results) Book (3 results)

  • [Journal Article] BMP-4 upregulates Kit expression in mouse melanoblasts prior to the Kit-dependent cycle of melanogenesis2008

    • Author(s)
      Kawakami T, et. al.
    • Journal Title

      Journal of Investigative Dermatology 128(5)

      Pages: 1220-1226

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Proteomic analysis of immature murine melanocytes at different stages of maturation:A crucial role for calreticulin2008

    • Author(s)
      Kawase A, et. al.
    • Journal Title

      Journal of Dermatological Science 49(1)

      Pages: 43-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] High titer of serum antiphospholipid antibodies levels in adult Henoch-Schonlein purpura and cutaneous leukocytoclastic angiitis2008

    • Author(s)
      Kawakami T, et. al.
    • Journal Title

      Arthritis&Rheumtism 59(4)

      Pages: 561-567

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] BMP-4 upregulates Kit expression in mouse melanoblasts prior to the Kit-dependent cycle of melanogenesis.2008

    • Author(s)
      Kawakami T
    • Journal Title

      J Invest Dermatol. 128(5)

      Pages: 1220-1226

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Proteomic analysis of immature murine melanocytes at different stages of maturation : A crucial role for calreticulin.2008

    • Author(s)
      Kawase A
    • Journal Title

      J Derrnatol Sci. 49(1)

      Pages: 43-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] High titer of serum antiphospholipid antibodies levels in adult Henoch-Schonlein purpura and cutaneous leukocytoclastic angiitis.2008

    • Author(s)
      Kawakami T
    • Journal Title

      Arthritis Rheum 59(4)

      Pages: 561-567

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of matrilysin(matrix metalloproteinase-7)in primary cutaneous and metastatic melanoma2007

    • Author(s)
      Kawasaki K, et. al.
    • Journal Title

      British Journal of Dermatology 156(4)

      Pages: 613-619

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sphingosine 1-phosphate accelerates wound healing in diabetic mice2007

    • Author(s)
      Kawanabe T, et. al.
    • Journal Title

      Journal of Dermatological Science 48(1)

      Pages: 53-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa2007

    • Author(s)
      Kawakami T, et. al.
    • Journal Title

      Arthritis&Rheumtism 57(8)

      Pages: 1507-1513

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] TGF-beta overexpression in cutaneous extramedullary hematopoiesis of a patient with myelodysplastic syndrome associated with myelofibrosis2007

    • Author(s)
      Kawakami T, et. al.
    • Journal Title

      Journal of The American Academy of Dermatology 58(4)

      Pages: 703-706

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of matrilysin(matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma.2007

    • Author(s)
      Kawasaki K
    • Journal Title

      Br J Dermatol. 156(4)

      Pages: 613-619

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sphingosine 1-phosphate accelerates wound healing in diabetic mice.2007

    • Author(s)
      Kawanabe T
    • Journal Title

      J Dermatol Sci. 48(1)

      Pages: 53-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa.2007

    • Author(s)
      Kawakami T
    • Journal Title

      Arthritis Rheum. 57(8)

      Pages: 1507-1513

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Transforming growth factor-beta overexpression in cutaneous extramedullary hematopoiesis of a patient with myelodysplastic syndrome associated with myelofibrosis.2007

    • Author(s)
      Kawakami T
    • Journal Title

      J Am Acad Dermatol. 58(4)

      Pages: 703-706

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Proteomic analysis of immature murine melanocytes at different stages of maturation: A crucial role for calreticulin.2007

    • Author(s)
      Kawase A, et. al.
    • Journal Title

      J Dermatol Sci 49(1)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa.2007

    • Author(s)
      Kawakami T, et. al.
    • Journal Title

      Arthritis Rheum. 57(8)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of matrilysin(matrix metalloproteinase-7)in primary cutane ous and metastatic melanoma.2007

    • Author(s)
      Kawasaki K, et. al.
    • Journal Title

      Br J Dermatol. 156(4)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of matrilysin(matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma.2007

    • Author(s)
      Kawakami T, er al.
    • Journal Title

      British Journal of Dermatology 156

      Pages: 613-619

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cutaneous manifestations in patient with microscopic polyangiitis. Minireview.2006

    • Author(s)
      Kawasaki K, et al.
    • Journal Title

      Acta Dermatol Venereol 86

      Pages: 144-147

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oral antihistamine therapy influences plasma tryptase levels in adult atopic dermatitis.2006

    • Author(s)
      Kawakami T, et al.
    • Journal Title

      Journal of Dermatological Science 43

      Pages: 127-134

    • NAID

      10020549041

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Elevated serum IgA anticardiolipin antibody levels in adult Henoch-Schonleinpurpura.2006

    • Author(s)
      Kawakami T, et al.
    • Journal Title

      British Journal of Dermatology 155

      Pages: 983-987

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 掻痒を伴う皮膚疾患患者に対するエバスチン(エバステル錠)の有効性の検討 DLQIによる患者QOLの評価2006

    • Author(s)
      相馬良直, 他
    • Journal Title

      新薬と臨床 55

      Pages: 1430-1438

    • Related Report
      2006 Annual Research Report
  • [Presentation] BMP-4 regulates melanocyte proliferation and differentiation in mouse neural crest cells just before they enter the Kit-dependent cycle of melanogenesis2007

    • Author(s)
      Kawakami T, et. al.
    • Organizer
      14th European Society for Pigment Cell Research
    • Place of Presentation
      Bari,Italy
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] BMP-4 regulates melanocyte proliferation and differentiation in mouse neural crest cells just before they enter the Kit-dependent cycle of melanogenesis2007

    • Author(s)
      Kawakami T, et. al.
    • Organizer
      14th European Society for Pigment Cell Research
    • Place of Presentation
      Bari, Italy
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] BMP-4 signalling regulates Kit expression in mouse neural crest cells prior to the Kit-dependent cycle of melanogenesis2007

    • Author(s)
      Kawasaki K, et. al.
    • Organizer
      the 14th Meeting for the European Society for Pigment Cell Research
    • Place of Presentation
      Bari, Italy
    • Related Report
      2007 Annual Research Report
  • [Book] 皮膚科診療プラクティス20巻 Enviromental Dermatology外的刺激によるメラニン合成の変調2007

    • Author(s)
      川上 民裕
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 環境・職業からみた皮膚疾患2007

    • Author(s)
      宮地 良樹、他
    • Total Pages
      347
    • Publisher
      文光堂
    • Related Report
      2007 Annual Research Report
  • [Book] 皮膚科診療のコツと落とし穴、(2)疾患I2006

    • Author(s)
      川上民裕
    • Total Pages
      8
    • Publisher
      最近の血管炎症候群-皮膚科医のかかわり方
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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