Ras Signaling, Deregulation of Gene Expression and Oncogenesis

Abstract

While our understanding of Ras signaling is significant and many of the signaling components and pathways activated by Ras have been delineated, it is also likely that much remains to be determined. The discovery of additional downstream effectors of Ras continues and reveals further diversity and complexity in the cytoplasmic signaling activities of Ras. The recent identification of PLC3 as a Ras effector links Ras activity directly to the actions of second messengers, calcium and diacylglycerol, that in turn cause pleotropic cellular responses. Conversely, some effectors of Ras (Nore1 and RASSF1) may promote apoptosis rather than oncogenesis. How these effectors may contribute to the mechanism of Ras-mediated oncogenesis will be important to establish. One major consequence of these diverse effector signaling events involves changes in gene expression. Some signaling events directly stimulate the activity of specific transcription factors and the number of these factors continues to increase. Other Ras-mediated signaling events, including DNA methylation or histone acetylation, may cause global changes in gene expression. The development and applications of methods, such as microarray analyses and functional proteomics, to evaluate global changes in gene or protein expression will further increase our knowledge of the gene targets of Ras. Hence, this area of Ras research will evolve rapidly in the coming years. The accumulation of information will certainly occur at a pace that greatly exceeds our ability to make sense of these observations. Nevertheless, our utilization of this information will facilitate important advances for understanding the role of Ras in oncogenesis and for the identification of novel therapeutic approaches for cancer diagnosis and treatment.