TRANSFORMING GENES OF AVIAN RNA TUMOR VIRUSES

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We are pursuing the study of the process by which viral oncogenes, as well as their collular homolgs, induce the activation of biochemical events that direct the cell towards malignant transformation and neoplasia. Utilizing retroviruses as tools to understand the structural and molecular nature of the cellular oncogenes transduced by these viruses has enabled the resolution of these details in both normal and malignant systems. Further, we have utilized these onc genes as probes revealing the genomic organization of myc and mht proto-oncogenes in a variety of cells, such as human, all the way down evolutionarily to fish and Drosophila. In addition to studying the genomic organization of the three retroviruses (MC29, MH2 and OK10), all part of the myc oncogene family, we have approached the organization of several dual oncoagene systems in an attempt to resolve the oncogenic interaction of genes mht and myc in MH2, and ets and myb in E26. Utilizing these probes has enabled us to expand our study to include the organization and expression of ets and myc in several human neoplasias which undergo chromosomal rearrangements. Additionally, we have constructed and utilized exapression vectors to produce large amounts of specific oncogene products and then to purify and characterize them chemically and immunologically, producing valuable immunodiagnostic reagents in the process. Further, our knowledge of the molecular structure of specific oncogenes has enabled us to make unique synthetic oligopeotides and produce cognate antisera to probe these relatively scarce proteins in normal cellular systems, which has led to their intracellular localization and cellular association. These studies on normal and activate oncogenes will have inportant diagonostic, as well as functional, implications towards understanding their role in the process of malignancy.