Immortalization by c-myc, H-ras, and Ela oncogenes induces differential cellular gene expression and growth factor responses

Mol Cell Biol. 1987 Nov;7(11):3899-907. doi: 10.1128/mcb.7.11.3899-3907.1987.

Abstract

Early-passage rat kidney cells were immortalized or rescued from senescence with three different oncogenes: viral promoter-driven c-myc, H-ras (Val-12), and adenovirus type 5 E1a. The normal c-myc and H-ras (Gly-12) were unable to immortalize cells under similar conditions. Quantitation of RNA in the ras-immortalized lines demonstrated that the H-ras oncogene was expressed at a level equivalent to that of the normal H-ras gene in established human or rat cell lines. Cell lines immortalized by different oncogenes were found to have distinct growth responses to individual growth factors in a short-term assay. E1a-immortalized cells were largely independent of serum growth factors, whereas c-myc-immortalized cells responded to serum better than to epidermal growth factor and insulin. H-ras-immortalized cells responded significantly to insulin alone and gave a maximal response to epidermal growth factor and insulin. Several cellular genes associated with platelet-derived growth factor stimulation, including c-myc, were expressed at high levels in the H-ras-immortalized cells, and c-myc expression was deregulated, suggesting that the H-ras oncogene has provided a "competence" function. H-ras-immortalized cells could not be morphologically transformed by secondary transfection with a long terminal repeat-c-myc oncogene, but secondary transfection of the same cells with H-ras (Val-12) produced morphologically transformed colonies that had 20- to 40-fold higher levels of H-ras oncogene expression. Thus, transformation in this system is dependent on high levels of H-ras oncogene expression rather than on the presence of activated H-ras and c-myc oncogenes in the same cell.

Publication types

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

MeSH terms

  • Adenovirus Early Proteins
  • Adenoviruses, Human / genetics*
  • Animals
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Genes*
  • Genes, Viral*
  • Genes, ras*
  • Oncogene Proteins, Viral / genetics*
  • Oncogenes*
  • Proto-Oncogenes*
  • Transcription, Genetic

Substances

  • Adenovirus Early Proteins
  • Oncogene Proteins, Viral