Gene expression profiling in melanoma identifies novel downstream effectors of p14ARF

Leisl M. Packer*, Sandra J. Pavey, Glen M. Boyle, Mitchell S. Stark, Ana L. Ayub, Helen Rizos, Nicholas K. Hayward

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Citations (Scopus)


p14ARF is inactivated by deletions/mutations in many cancer types and can suppress cell growth by both p53-dependent and p53-independent mechanisms. To identify novel downstream effectors of p14ARF, we used gene expression profiling as a primary screening tool to select candidates for follow up validation studies using in vitro cell-based assays. Gene expression profiles of a panel of 35 melanoma cell lines with either wild-type (n = 12) or mutant (n = 23) p14ARF were compared to identify genes associated with inactivation of p14ARF. Analysis of the microarray data identified 1,316 probe sets that were significantly (p < 0.01) differentially expressed between the p14ARF wild-type and mutant cell lines. Pathway analysis of these genes showed an overrepresentation of many receptor-mediated signal transduction pathways, e.g. TGFβ, EGF, HGF, PDGF, MAPK, Wnt and integrin pathways. A number of components of these pathways, including FLRT3, RUNX2, MIG-6 and SMURF2 were confirmed as downstream targets of p14ARF using p14ARF-inducible cell lines and RNAi. We propose that regulation of these genes may contribute to melanoma development when p14ARF function is lost.

Original languageEnglish
Pages (from-to)784-790
Number of pages7
JournalInternational Journal of Cancer
Issue number4
Publication statusPublished - 15 Aug 2007
Externally publishedYes


  • FLRT3
  • Melanoma
  • Microarray
  • p14ARF
  • RUNX2

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