Overexpression of Collagenase 1 (MMP-1) Is Mediated by the ERK Pathway in Invasive Melanoma Cells: ROLE OF BRAF MUTATION AND FIBROBLAST GROWTH FACTOR SIGNALING

作者:Huntington, J. T.; Shields, J. M.; Der, C. J.; Wyatt, C. A.; Benbow, U.; Slingluff, C. L.; Brinckerhoff, C. E. 刊名:Journal of Biological Chemistry 上传者:李思萌

【摘要】http://www.jbc.org/cgi/doi/10.1074/jbc.M405102200

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Overexpression of Collagenase 1 (MMP-1) Is Mediated by the ERK Pathway in Invasive Melanoma Cells ROLE OF BRAF MUTATION AND FIBROBLAST GROWTH FACTOR SIGNALING* Received for publication, May 7, 2004, and in revised form, June 1, 2004 Published, JBC Papers in Press, June 7, 2004, DOI 10.1074/jbc.M405102200 Jonathan T. Huntington?§, Janiel M. Shields?, Channing J. Der?, Colby A. Wyatt, Ulrike Benbow**??, Craig L. Slingluff, Jr.§§, and Constance E. Brinckerhoff**?? From the Norris Cotton Cancer Center, Departments of ?Physiology, **Medicine, and Biochemistry, Dartmouth Medical School, Lebanon NH 03756, the ?Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, and the §§Department of Surgery, University of Virginia, Charlottesville, Virginia 22908 Melanoma progresses as a multistep process where the thickness of the lesion and depth of tumor invasion are the best prognostic indicators of clinical outcome. Degradation of the interstitial collagens in the extracellular matrix is an integral component of tumor invasion and metastasis, and much of this degradation is mediated by collagenase-1 (MMP-1), a member of the matrix metalloproteinase (MMP) family. MMP-1 levels increase during melanoma progression where they are associated with shorter disease-free survival. The Ras/Raf/ MEK/ERK mitogen-activated protein kinase (MAPK) pathway is a major regulator of melanoma cell proliferation. Recently, BRAF has

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