Gene expression profiling of tumours derived from rasV12/E1A-transformed mouse embryonic fibroblasts to identify genes required for tumour development.
BACKGROUND
In cancer, cellular transformation is followed by tumour development. Knowledge on the mechanisms of transformation, involving activation of proto-oncogenes and inactivation of tumour-suppressor genes has considerably improved whereas tumour development remains poorly understood. An interesting way of gaining information on tumour progression mechanisms would be to identify genes whose expression is altered during tumour formation. We used the Affymetrix-based DNA microarray technology to analyze gene expression profiles of tumours derived from rasV12/E1A-transformed mouse embryo fibroblasts in order to identify the genes that could be involved in tumour development.


RESULTS
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.


CONCLUSIONS
Some of the genes identified in this work, whose expression is altered upon rasV12/E1A transformation of MEFs, could be new cancer therapeutic targets.
Vasseur
Sophie
S
INSERM U,624, Stress Cellulaire, 163 Avenue de Luminy, Case 915, Parc Scientifique et Technologique de Luminy, 13288 Marseille Cedex 9, France. vasseur@marseille.inserm.fr <vasseur@marseille.inserm.fr>
Malicet
Cédric
C
Calvo
Ezequiel L
EL
Dagorn
Jean Charles
JC
Iovanna
Juan L
JL
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
D017500:Adenovirus E1A Proteins; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D015689:Oncogene Protein p21(ras)