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Immortalization of primary cells by DNA tumor viruses
1Department of Oncology, Radiumhemmet, Karolinska Institute and Hospital, Stockholm, Sweden.
Abstract:
Cellular senescence is characterized by a decline in sensitivity to growth factors resulting in cessation of cellular growth. The expression of cellular or viral oncogenes may result in the establishment of cell lines with unlimited proliferative potential ("immortalization"). A variety of viral and cellular oncogenes have been reported to immortalize cells, suggesting that multiple mechanisms may lead to an escape from senescence. Immortalization has been reported to occur as a result of an interaction of viral proteins with cellular suppressor gene products or may result from the elevated expression of "transforming" oncoproteins (such as the polyomavirus middle-t antigen). Here we speculate that a selection for cells with a further decreased probability of cell cycle withdrawal can occur during the growth of cells expressing viral early genes, resulting in a process of tumor progression. Explaining immortalization in terms of mitogenic stimulation due to the expression of viral oncogenes followed by genetic/epigenetic changes may help to explain why lytic DNA viruses have a biological activity which may not be necessary for their life cycle.
Insights
Cellular senescence halts cell growth, but oncogenes can cause immortalization. Viral oncogenes may drive tumor progression by decreasing cell cycle withdrawal, explaining viral activity beyond their life cycle.
Area of Science:
- Cellular and Molecular Biology
- Oncology
- Virology
Background:
- Cellular senescence is a state of irreversible growth arrest triggered by various stressors.
- Oncogene expression can override senescence, leading to cellular immortalization.
- Viral oncogenes are known to interfere with cellular suppressor gene products or elevate oncoprotein expression.
Purpose of the Study:
- To explore the mechanisms by which viral oncogenes contribute to cellular immortalization.
- To investigate the potential role of viral oncogenes in tumor progression through decreased cell cycle withdrawal.
- To provide a framework for understanding the biological activity of lytic DNA viruses in relation to their life cycle.
Main Methods:
- Literature review and theoretical speculation on oncogene function and cellular senescence.
- Analysis of known interactions between viral proteins and cellular suppressor genes.
- Examination of the impact of elevated oncoprotein expression on cell cycle regulation.
Main Results:
- Viral and cellular oncogenes can lead to immortalization through diverse mechanisms.
- Selection for cells with reduced cell cycle withdrawal probability during viral gene expression can drive tumor progression.
- This model may explain why some viruses exhibit biological activities not essential for their replication.
Conclusions:
- Oncogene-induced immortalization represents an escape from senescence.
- Viral oncogenes play a critical role in promoting tumor progression by altering cell cycle control.
- The proposed model offers insights into the non-essential biological activities of certain viruses.