Gene expression profiling of tumours derived from rasV12/E1A-transformed mouse embryonic fibroblasts to identify genes required for tumour development

Among the 12,000 genes analyzed in this study, only 489 showed altered expression during tumour development, 213 being up-regulated and 276 down-regulated. The genes differentially expressed are involved in a variety of cellular functions, including control of transcription, regulation of mRNA maturation and processing, regulation of protein translation, activation of interferon-induced genes, intracellular signalling, apoptosis, cell growth, angiogenesis, cytoskeleton, cell-to-cell interaction, extracellular matrix formation, metabolism and production of secretory factors.Some of the genes identified in this work, whose expression is altered upon rasV12/E1A transformation of MEFs, could be new cancer therapeutic targets.Cellular transformation is a complex process which involves activation of proto-oncogenes and inactivation of tumour-suppressor genes [1]. After transformation, the cells can generate malignant tumours, by mechanisms only partly understood yet. It is supposed that some modifications in the pattern of gene expression will promote survival of transformed cells in situ, other modifications will favour eventual formation of metastases [2], the capacity to adapt a new microenvironment being of major importance for successful tumour development and progression [reviewed in [3]]. Therefore, identification of genes whose expression is altered during tumour formation should provide important information on the underlying molecular mechanisms. In the present work, we used the Affymetrix-based DNA microarray technology to analyze gene expression profiles of tumour-derived from rasV12/E1A-transformed primary mouse embryonic fibroblasts (MEFs), in order to identify genes associated with tumour development.The ras oncogene can transform most immortalized rodent cells to generate tumour cells, whereas transformation of primary cells requires either a cooperating oncogene or the inactivation of a tumour suppressor gene. The adenovirus E1A oncogene cooperates with r