Transcriptional Programs Following Genetic Alterations in p53 and H-Ras Genes

摘要

The difficulty to dissect a complex phenotype of established malignant cells to a number of critical transcriptional programs greatly impends our understanding of the malignant transformation. We took the advantage of the global genomic profiling approach and tried to go one step further in the dissection of the transformation network. We sought to identify the genetic signatures and key target genes, which underlie the genetic alterations in p53 and H-Ras introduced into primary human fibroblasts. A genome wide expression profiling identified distinct genetic targets corresponding to the genetic alterations listed above. Genes associated with angiogenesis and invasiveness were mostly induced upon genetic alterations in the p53 and H-Ras. Deciphering these transformation fingerprints, which are affected by the most common oncogenic mutations, provides considerable insight into regulatory circuits controlling malignant transformation and will, hopefully, open new avenues for rational therapeutic decisions.