Differential regulation of gene expression in human melanoma cells overexpressing catalase

IRENE IBAÑEZ; CANDELARIA BRACALANTE; HEBE DURAN; ARIEL CHERNOMORETZ

Congreso; Free radicals 2013- VIII Meeting of the Society Free Radical Biology and Medicine-South American Group; 2013

Society Free Radical Biology and Medicine-South American Group

Differential gene expression among human amelanotic melanoma cells, A375, and two established catalase-overexpressing clones with different phenotypes (A7, melanotic and non-invasive and G10, amelanotic and invasive) was evaluated by the bioinformatic analysis of whole genome microarrays (Affymetrix). The analysis was performed by the R programming language and different tools of Bioconductor (parameters: lfc=1 and p<0.001). Differential genes were functionally classified by DAVID (Database for Annotation, Visualization and Integrated Discovery). Significant and concordant differences between phenotypes were evaluated by GSEA (Gene Set Enrichment Analysis) with an a priori defined gene sets collected from Gene Ontology Database (131 gene groups) and KEGG (Kyoto Encyclopedia of Genes and Genomes) (19 gene groups). A7 showed gene sets up-regulated in processes like melanogenesis, cell adhesion and peroxisome whereas G10 exhibited gene sets up-regulated in neural crest cell migration, endothelial cell migration and angiogenesis in both analysis. MELANA, TYR and OCA2 genes, associated with melanocytic differentiation, were up-regulated in A7 while they were described as down-regulated in aggressive melanomas. PMP22, FLRT3 and NRCAM genes, associated with invasive melanomas, were up-regulated in G10. In conclusion, the phenotypes of both clones could be associated with different compensation of catalase overexpression that triggers differential regulation of gene expression.