TRANSFORMING GENES OF AVIAN RNA TUMOR VIRUSES

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A major effort of the LMO is to elucidate the processes by which specific retroviral oncogenes, as well as their cellular homologs, are able to impact on critical cellular events. The oncogene elements, derived from avian leukemia viruses, have been intensively investigated and analyzed to define their structural and genomic organization. Using the oncogenes myc, mht and ets as probes, we have detected, isolated and cloned the cellular homologs of these genes from evolutionarily diverse organisms such as humans, mice, cats, fish, sea urchin and Drosophila. Specific regions of these cellular genes are retained at high levels of homology and each was compared and examined, as was its expressed product. In all cases, the proto-oncogenes were significantly larger than their corresponding viral oncogenes. This consistent truncation of the viral oncogene and its products may implicate this as a general mechanism in the critical events controlled and regulated by these highly conserved genes. We have also developed and exploited several expression vector systems, both prokaryotic and eukaryotic, to produce oncogene-specific products in quantity. These products were used to purify, characterize and develop immunologic reagents to locate the cellular proto-oncogene products, and characterize their molecular structure. Such reagents have also been used to probe for the expression of oncogene-specific products in normal and malignant tissues and related them to specific human pathologies. In certain leukemias we have noted an alteration in the pattern of expression of the ets genes, compared to the expression in normal blood cells. These studies may have a useful application in the diagnostic and clinical evaluation of malignancy and how the cell progresses into neoplasia.