Enforced expression of the c-myc oncogene inhibits cell differentiation by precluding entry into a distinct predifferentiation state in G/sub 0//G/sub 1/
A broad base of data has implicated a role for the c-myc proto-oncogene in the control of the cell cycle and cell differentiation. To further define the role of myc in these processes, the authors examined the effect of enforced myc expression on several events that are thought to be important steps leading to the terminally differentiated state: (i) the ability to arrest growth in G/sub 0//G/sub 1/, (ii) the ability to replicate the genome upon initiation of the differentiation program, and (iii) the ability to loose responsiveness to mitogens and withdraw from the cell cycle. 3T3-L1 preadipocyte cell lines expressing various levels of myc mRNA were established by transfection with a recombinant myc gene under the transcriptional control of the Rous sarcoma virus (RSV) promoter. Cells that expressed high constitutive levels of pRSV myc mRNA arrested in G/sub 0//G/sub 1/ at densities similar to those of normal cells at confluence. Upon initiation of the differentiation program, such cells traversed the cell cycle with kinetics similar to those of normal cells and subsequently arrested in G/sub 0//G/sub 1/. Thus, enforced expression of myc had no effect on the ability of cells to arrest growth in G/sub 0//G/sub 1/ or to replicate the genome upon initiation of the differentiation program. Cells were then tested for their ability to reenter the cell cycle upon exposure to high concentrations of serum and for their capacity to differentiate. In contrast to normal cells, cells expressing high constitutive levels of myc RNA reentered the cell cycle when challenged with 30% serum and failed to terminally differentiate.
- Research Organization:
- Dept. of Biological Chemistry and Program in Cellular and Molecular Biology, Univ. of Michigan Medical School, Ann Arbor, MI (US)
- OSTI ID:
- 6994636
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 8:4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CELL DIFFERENTIATION
GENETIC CONTROL
MESSENGER-RNA
RNA PROCESSING
ONCOGENES
BIOLOGICAL PATHWAYS
MOLECULAR BIOLOGY
ONCOGENIC VIRUSES
HOST-CELL REACTIVATION
CELL CULTURES
CELL CYCLE
CELL PROLIFERATION
DNA REPLICATION
GENE RECOMBINATION PROTEINS
MITOGENS
ONCOGENIC TRANSFORMATIONS
PHENOTYPE
TRANSCRIPTION
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL TRANSFORMATIONS
CONTROL
GENES
MICROORGANISMS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PARASITES
PEST CONTROL
PROTEINS
RECOVERY
REPAIR
RNA
VIRUSES
550400* - Genetics
550200 - Biochemistry
550300 - Cytology