The oncogenes (v-oncgenes) of rapidly transforming retroviruses have homologs (c-oncgenes) in the genomes of normal cells. In this study, we characterized and quantitated transcription from four c-oncgenes, c-myb, c-myc, c-erb, and c-src, in a variety of chicken cells and tissues. Electrophoretic analysis of polyadenylated RNA, followed by transfer to nitrocellulose and hybridization to clonedoncprobes showed that c-myb, c-myc, and c-srceach give rise to a single mature transcript, whereas c-erbgives rise to multiple transcripts (B. Vennstrom and J. M. Bishop, Cell, in press) which vary in abundance among different cells and tissues. Transcription from c-myb, c-myc, c-erb, and c-srcwas quantitated by a “dot-blot” hybridization assay. We found that c-myc, c-erb, and c-srctranscription could be detected in nearly all cells and tissues examined, whereas c-mybtranscription was detected only in some hemopoietic cells; these cells, however, belong to several different lineages. Thus, in no case was expression of a c-oncgene restricted to a single cell lineage. There appeared to be a correlation between levels of c-mybexpression and hemopoietic activity of the tissues and cells examined, which suggests that c-mybmay be expressed primarily in immature hemopoietic cells. An examination of c-oncRNA levels in target cells and tissues for viruses carrying the corresponding v-oncgenes revealed no obvious correlation, direct or inverse, between susceptibility to transformation by a given v-oncgene and expression of the homologous c-oncgene.

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This study addressed the possibility that proto-myb (also called c-myb), the cellular homolog of a retroviral transforming gene, plays a role in hemopoiesis, particularly during maturation of T cells. By gel blot hybridization, we confirmed previous reports that proto-myb transcripts are found at much higher levels in thymic lymphocytes and cells of the erythroid lineage than in other tissue sources. Using dot blot hybridizations, we demonstrated further that similar levels of proto-myb expression are found in thymic lymphocytes taken from young mice with active thymuses and from old mice whose thymuses have undergone involution and that the extent of proto-myb expression decreases at least 10-fold as T cells progress from immature cortical thymocytes to the mature, resting T cells taken from lymph nodes. These results suggest that the protein product of proto-myb functions during T-cell differentiation.

The chicken genome contains nucleotide sequences homologous to the transforming genes (oncogenes) of a number of avian retroviruses. We have isolated chicken DNA (c-myc) that is homologous to the oncogene (v-myc) of the avian myelocytomatosis virus MC29 and have compared the structures of the cellular and viral genes. Results from restriction endonuclease mapping of c-myc and from analysis of heteroduplexes between the DNAs of the cellular and viral genes show that c-myc is homologous to 1,500 nucleotides in v-myc DNA. This homologous region is interrupted in c-myc by an intron-like sequence of 1,100 nucleotides which is absent from v-myc. Nuclear RNA from normal chicken cells contains at least five species of transcripts from c-myc ranging from 2.5 to 6.5 kilobases in length. By contrast, cytoplasm contains only the 2.5-kilobase c-myc RNA. These features of the c-myc gene and its nuclear transcripts are characteristic of normal cellular genes and suggest that the myc gene is of cellular rather than viral origin. The exons in c-myc may define two functional domains in the gene and may therefore facilitate the dissection of the different oncogenic potentials of the MC29 virus.