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

Journal Article · Sat Oct 31 23:00:00 EST 1987 · Mol. Cell. Biol.; (United States)

DOI:https://doi.org/10.1128/MCB.7.11.3899· OSTI ID:7070729

Kelekar, A; Cole, M D

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), Journal Name: Mol. Cell. Biol.; (United States) Vol. 7:11; ISSN MCEBD
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
550300 -- Cytology
59 BASIC BIOLOGICAL SCIENCES
ADENOVIRUS
ANIMAL CELLS
ANIMALS
BIOLOGICAL FUNCTIONS
BIOLOGICAL PATHWAYS
BODY
CELL CULTURES
CELL PROLIFERATION
CELL TRANSFORMATIONS
CLONING
DNA
DNA-CLONING
FUNCTIONS
GENES
GROWTH FACTORS
KIDNEYS
MAMMALS
MICROORGANISMS
MITOGENS
MOLECULAR BIOLOGY
NUCLEIC ACIDS
ONCOGENES
ONCOGENIC TRANSFORMATIONS
ONCOGENIC VIRUSES
ORGANIC COMPOUNDS
ORGANS
PARASITES
PHENOTYPE
PROTEINS
RATS
RECOMBINANT DNA
RODENTS
SOMATIC CELLS
VERTEBRATES
VIRUSES