c-Myc Interacts with Hypoxia to Induce Angiogenesis <b> <i>In vivo</i> </b> by a Vascular Endothelial Growth Factor-Dependent Mechanism

DOI PDF 被引用文献2件
  • Ulrike E. Knies-Bamforth
    1Molecular Oncology Laboratory and
  • Stephen B. Fox
    3Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; and
  • Richard Poulsom
    2Histopathology Unit, Cancer Research United Kingdom, Weatherall Institute for Molecular Medicine, and
  • Gerard I. Evan
    4Cancer Research Institute, University of California, San Francisco, California
  • Adrian L. Harris
    1Molecular Oncology Laboratory and

抄録

<jats:title>Abstract</jats:title> <jats:p>The proto-oncogene c-myc is involved in the regulation of cell proliferation, differentiation, and apoptosis. In this study, we used an inducible transgenic mouse model in which c-Myc was targeted to the epidermis and, after activation, gave rise to hyperplastic and dysplastic skin lesions and to dermal angiogenesis, involving both vascular endothelial growth factor (VEGF) receptor-1 and VEGF receptor-2. After c-Myc activation, VEGF mRNA was expressed in postmitotic keratinocytes where it colocalized with transgene expression and areas of tissue hypoxia, suggesting a role of hypoxia in VEGF induction. In vitro, c-Myc activation alone was able to induce VEGF protein release and in conjunction with hypoxia, c-Myc activation further increased VEGF protein. Blocking VEGF signaling in vivo significantly reduced dermal angiogenesis, demonstrating the importance of VEGF as a mediating factor for the c-Myc–induced angiogenic phenotype.</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 64 (18), 6563-6570, 2004-09-15

    American Association for Cancer Research (AACR)

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