RAS and PKA pathways in cancer: new insight from transcriptional analysis.

ABSTRACT

Through its ability to regulate the activity of a large number of transcription factors, the Ras pathway is able to control several transcriptional programs leading to proliferation, differentiation, metabolism, cytoskeletal reorganization and immune response. Cyclic AMP (cAMP) is a ubiquitous intracellular second messenger whose major intracellular target in eukaryotes is protein kinase A (PKA). Wide evidence for cross talk between the Ras and cAMP-PKA pathways is available. After reviewing some features of Ras and PKA signalling that are relevant for cancer biology, we re-analyze available genome-wide expression data for genes encoding proteins of the downstream branch of the PKA pathway in human tumor cell lines as a function of the mutational state of the Ras pathway. The observed Ras-dependent pattern of regulation of the analyzed genes may contribute to explain how the cAMP-PKA axis is involved in oncogenic processes induced by Ras.