ANALYSIS OF THE CELLULAR ONCOGENE PROTO-MYB

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A host origin for retroviral oncogenes is implied by the discovery that vertebrate DNA contains highly conserved genes ("proto-oncogenes") that are homologous to retroviral oncogenes. The similarity between viral oncogenes and proto-oncogenes implies a normal role for proto-oncogenes in cell growth and/or differentiation. Our long-term goal is to elucidate the presumptive roles of proto-oncogenes as cancer genes and as regulators of normal cell growth. To that effect, we have conducted studies focused primarily on the expression of proto-myb, a proto-oncogene that corresponds to the transforming gene of the avian myeloblastosis virus. In current studies with mice, we have shown that proto-myb expression is confined exclusively to cells in early stages of differentiation in the hemopoietic lineages and that the highest level of proto-myb mRNA observed was that seen in the thymus. In other experiments, we have ruled out any correlation between expression of several proto-oncogenes and thymic involution. Preliminary results with cultured cells suggest furthermore that proto-myh mRNA levels are not dependent on the proliferative state of the cells. At present, our efforts are directed primarily towards cloning and characterizing the mouse proto-myb gene. By screening a library of mouse DNA in phage lambda, we have obtained clones of genome DNA that evidently contain the 5' end of the proto-myb gene. We have also isolated a cDNA clone containing 2.5 kb of sequence, most of which extends 3' of the cloned genome DNA. By restriction mapping, we have estimated a size of 40 Kb for the mouse proto-myb gene. Selected portions of the cloned DNAs are currently being sequenced. Additional efforts are underway to clone the remainder of the proto-myb gene and to study proto-myb expression thymocytes exposed to mitogens and hormones. (P)