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Met amplification and tumor progression in Cdkn2a ‐deficient melanocytes
Author(s) -
VanBrocklin Matthew W.,
Robinson James P.,
Whitwam Todd,
Guilbeault Adam R.,
Koeman Julie,
Swiatek Pamela J.,
Vande Woude George F.,
Khoury Joseph D.,
Holmen Sheri L.
Publication year - 2009
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2009.00576.x
Subject(s) - cdkn2a , melanoma , cancer research , tumor progression , biology , receptor tyrosine kinase , signal transduction , gene , genetics
Summary While many genetic alterations have been identified in melanoma, the relevant molecular events that contribute to disease progression are poorly understood. Most primary human melanomas exhibit loss of expression of the CDKN2A locus in addition to activation of the canonical mitogen‐activated protein kinase signaling pathway. In this study, we used a Cdkn2a ‐deficient mouse melanocyte cell line to screen for secondary genetic events in melanoma tumor progression. Upon investigation, intrachromosomal gene amplification of Met , a receptor tyrosine kinase implicated in melanoma progression, was identified in Cdkn2a ‐deficient tumors. RNA interference targeting Met in these tumor cells resulted in a significant delay in tumor growth in vivo compared with the control cells. MET expression is rarely detected in primary human melanoma but is frequently observed in metastatic disease. This study validates a role for Met activation in melanoma tumor progression in the context of Cdkn2a deficiency.