myc protooncogene linked to retroviral promoter, but not to enhancer, transforms embryo cells.

Abstract

To define conditions under which the chicken protooncogene p-myc is converted to a viral and possibly to a cellular transforming gene, we assayed transforming function of hybrid genes put together from cloned retroviral and p-myc elements and of p-myc genes isolated from spontaneous viral lymphomas. Transforming function was measured in quail embryo cells transfected with cloned myc genes. We found that only myc genes with a promoter of a retroviral long terminal repeat (LTR) located between the native p-myc promoter and the second p-myc exon have transforming function. Transforming efficiencies decreased with increasing lengths of unspliced sequences between the LTR and p-myc exon 2. p-myc DNAs with LTRs downstream of the coding region or upstream but in the opposite transcriptional orientation failed to transform embryo cells. Likewise, only those retroviral-p-myc combinations from chicken B-cell lymphomas with a LTR positioned as promoter upstream of p-myc exon 2 had transforming function. We conclude that substitution of a retroviral LTR for the promoter and for as yet poorly defined, untranscribed regulatory elements of p-myc is sufficient to convert chicken p-myc to a transforming gene. However, retroviral LTRs can only convert p-myc genes to embryo-cell-transforming genes from a limited number of positions, and not as position-independent enhancers. Further, we deduce that there are two classes of viral chicken B-cell lymphomas, those with and those without embryo-cell-transforming p-myc genes.

Unmutated proto-src coding region is tumorigenic if expressed from the promoter of Rous sarcoma virus: implications for the gene-mutation hypothesis of cancer.

“…These experiments confirm and extend studies with other proto-onc genes, which have demonstrated that about 100-fold increased expression from retrovirus promoters is sufficient for transforming function of diploid cells and tumorigenicity. Examples include retrovirus-promoted coding regions of proto-ras (3,16,18,20,21) and proto-myc (17,19,29). Thus, our experiments support the hypothesis that retroviral onc genes derive transforming function from strong viral promoters rather than from mutations that affect the coding sequence of native proto-onc genes (2,11).…”

“…However, transforming function of typical retroviral onc genes, including src, myc, and ras genes, was recently shown to depend on retroviral promoters rather than on the mutations that set apart the coding regions of viral and proto-onc genes (3,(16)(17)(18)(19)(20)(21). These promoters increase expression about 100-fold compared to the corresponding proto-onc genes (11,21,22).…”

Chromosome abnormalities and oncogenesis in cat leukemias

“…Activation of the proto-one genes, for example the p-myc, happens when the provirus integrates between the native p-myc promoter and the second exon of the p-myc as already mentioned (Zhou and Duesberg, 1988).…”

“…generate recombinant genes capable of transforming diploid cells (Zhou and Duesberg, 1988;Onions et al, 1987). Such genes may be cellular cancer genes.…”

“…The one gene hypothesis promoter and the second c-myc exon (Zhou and Duesberg, 1988); d) there are not diploid tumors isolated today with activated c-myc (Duesberg, 1987 b).…”