RAS and PKA pathways in cancer: new insight from transcriptional analysis.
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.
Chiaradonna
Ferdinando
F
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy. ferdinando.chiararadonna@unimib.it
Balestrieri
Chiara
C
Gaglio
Daniela
D
Vanoni
Marco
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D018631:ras Proteins; D000262:Adenylyl Cyclases