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Published on: May 15, 2020
Cellular regulation of mammalian sarcoma virus expression: a gene regulation model for oncogenesis
Abstract:
Investigations aimed at defining cellular functions required for expression of transformation by mammalian sarcoma viruses have led to the isolation of a class of revertants that contain biologically active feline sarcoma virus, yet possess in vitro and in vivo properties of normal cells. The block to expression of the transformed state in these cellular revertants was spontaneously reversible at low frequency. Moreover, infection with certain helper viruses reversed the block at very high efficiency. Helper virus complementation was shown not to be a direct effect of helper virus functions expressed in the initially infected revertant cell. Rather, the helper virus acted indirectly by rescuing sarcoma virus and allowing it to infect and transform another cell within the revertant population. Using biochemical and immunologic techniques, it was possible to demonstrate a specific and very marked reduction in transcriptional and translational products of the sarcoma viral genome in the revertant cells. Findings that the reversal of this block was associated with reacquisition of the transformed phenotype, together with other evidence, suggest that reversion results from cellular transcriptional regulation of the integrated sarcoma virus genome. Reversion in this virus transformation system provides a model for oncogenesis resulting from derepression of cellular genes that possess malignant potential.
Insights
Cellular revertants of feline sarcoma virus transformation show blocked viral gene expression. Helper viruses indirectly rescue sarcoma virus, enabling transformation and revealing cellular transcriptional regulation as a model for oncogenesis.
Area of Science:
- Virology
- Molecular Biology
- Cancer Research
Background:
- Mammalian sarcoma viruses induce cell transformation.
- Cellular revertants of transformation retain biologically active virus but exhibit normal cellular properties.
- The block to transformation in revertants is spontaneously reversible and highly sensitive to helper virus infection.
Purpose of the Study:
- To investigate the mechanisms underlying cellular transformation by sarcoma viruses.
- To identify cellular factors regulating the expression of viral oncogenes.
- To understand the role of helper viruses in modulating transformation and reversion.
Main Methods:
- Isolation and characterization of cellular revertants of feline sarcoma virus transformation.
- Analysis of viral gene expression using biochemical and immunologic techniques.
- Investigation of helper virus complementation and its indirect mechanism of action.
Main Results:
- Revertant cells exhibited significantly reduced transcriptional and translational products of the sarcoma viral genome.
- Helper virus infection did not directly affect revertant cells but rescued sarcoma virus to infect and transform other cells.
- Reversal of the transformation block was associated with reacquisition of the transformed phenotype.
Conclusions:
- Cellular transcriptional regulation of the integrated sarcoma virus genome is responsible for reversion.
- This virus transformation system provides a model for oncogenesis via derepression of cellular genes with malignant potential.
- Understanding these regulatory mechanisms is crucial for cancer research.
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