Gene expression profiling in melanoma identifies novel downstream effectors ofp14ARF
| Autor: | Ana L. Ayub, Leisl M. Packer, Nicholas K. Hayward, Sandra Pavey, Helen Rizos, Glen M. Boyle, Mitchell S. Stark |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Membrane Glycoproteins Microarray analysis techniques Cell growth Gene Expression Profiling Mutant Wnt signaling pathway Membrane Proteins Core Binding Factor Alpha 1 Subunit Biology Models Biological Gene expression profiling Oncology RNA interference Mutation Tumor Suppressor Protein p14ARF Gene expression Tumor Cells Cultured Cancer research Humans Signal transduction Melanoma Oligonucleotide Array Sequence Analysis Signal Transduction |
| Zdroj: | International Journal of Cancer. 121:784-790 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.22725 |
| Popis: | 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. TGF, 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. © 2007 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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