Met amplification and tumor progression in Cdkn2a-deficient melanocytes

Matthew W. VanBrocklin, James P. Robinson, Todd Whitwam, Adam R. Guilbeault, Julie Koeman, Pamela J. Swiatek, George F. Vande Woude, Joseph D. Khoury, Sheri L. Holmen

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)454-460
Number of pages7
JournalPigment Cell and Melanoma Research
Volume22
Issue number4
DOIs
StatePublished - Aug 2009

Keywords

  • Cdkn2a
  • Melanocytes
  • Met
  • Progression
  • Transformation

Fingerprint Dive into the research topics of 'Met amplification and tumor progression in Cdkn2a-deficient melanocytes'. Together they form a unique fingerprint.

Cite this