BIOLOGIC PROTERTIES OF NUCLEAR ONCOGENES

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Recent developments in application of molecular biology to epithelial cancers have led to the identification of specific genetic lesions resulting in either activation or inactivation of key target genes. These genes, called oncogenes, are involved in various aspects in the regulation of cell growth and as such play major roles in the early carcinogenic processes of "initiation" and "promotion". It is now critical to understand the precise mechanism by which these genes function so molecular or pharmacologic agents can ultimately be derived to alter or repress their effects. We have chosen to explore the biologic and biochemical functions of 2 dominant oncogenes (L-myc and c-jun). Transcriptional and translational products of L-myc may been characterized and correlated with biologic functions. In addition, hybrid molecules between c-myc and L-myc have been made to characterize the differences between these two family members. Ultimately, structure-function analysis for these genes will be determined. Likewise, we have recently described the transforming function of c-jun in mammalian cells and have now mapped this function by deletion mutation. Regions important for transformation and transactivation include an N-terminal transactivation domain, DNA binding region, and the leucine zipper domain. In addition, comparisons of c-jun with Jun B transactivation and transformation activities will be undertaken to understand the difference between these genes.