Immortalization by c-myc, H-ras, and Ela oncogenes induces differential cellular gene expression and growth factor responses
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.
- Research Organization:
- Dept. of Microbiology and Immunology, Duke Univ. Medical School, Durham, NC 27710 (USA)
- OSTI ID:
- 7070729
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 7:11
- Country of Publication:
- United States
- Language:
- English
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GROWTH FACTORS
BIOLOGICAL FUNCTIONS
ONCOGENES
RECOMBINANT DNA
SOMATIC CELLS
ADENOVIRUS
CELL CULTURES
DNA-CLONING
KIDNEYS
ONCOGENIC TRANSFORMATIONS
PHENOTYPE
RATS
ANIMAL CELLS
ANIMALS
BODY
CELL TRANSFORMATIONS
CLONING
DNA
FUNCTIONS
GENES
MAMMALS
MICROORGANISMS
MITOGENS
NUCLEIC ACIDS
ONCOGENIC VIRUSES
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550200* - Biochemistry
550300 - Cytology