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

Proc Natl Acad Sci U S A. 1988 May;85(9):2924-8. doi: 10.1073/pnas.85.9.2924.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic*
  • Cell Transformation, Viral
  • Chick Embryo
  • DNA Restriction Enzymes / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Enhancer Elements, Genetic*
  • Lymphoma / genetics
  • Lymphoma / microbiology
  • Promoter Regions, Genetic*
  • Proto-Oncogenes
  • Quail
  • Repetitive Sequences, Nucleic Acid
  • Retroviridae / genetics*
  • Transcription, Genetic

Substances

  • DNA Restriction Enzymes