NONNUCLEAR ONCOGENES AND THE REGULATION OF GENE-EXPRESSION IN TRANSFORMED-CELLS

Oncogene products not localized to the nucleus regulate the expression of a diverse group of genes. The identities of genes regulated by non-nuclear oncogenes can supply insights into the changes at the cellular level that accompany the altered expression of such genes during the multi-step process of carcinogenesis. For example, one set of genes whose expression is affected by non-nuclear oncogenes are genes encoding extracellular proteases and components of the extracellular matrix. The expression of these genes during tumorigenesis could have important consequences for tumor invasiveness and metastasis. Genes regulated by non-nuclear oncogenes also define signal transduction pathways that allow communication between the plasma membrane and the nucleus. Oncogene-regulated nuclear targets provide a tool to approach the problem of cellular signal transduction and may contribute a clearer view of intracellular signaling pathways and the interactions between these pathways during cell growth and differentiation. Studying the regulation of these genes has revealed that c-jun and members of the ets family of transcription factors are important nuclear targets for the action of several non-nuclear oncogenes. This approach has also indicated that ras p21 is necessary for selective signal transduction events mediated by receptor and nonreceptor tyrosine kinases, including the colony-stimulating factor 1 (CSF-1) receptor, the product of the c-fms gene.