Immortalization of primary cells by DNA tumor viruses.
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.
Linder
S
S
Department of Oncology, Radiumhemmet, Karolinska Institute and Hospital, Stockholm, Sweden.
Marshall
H
H
D000818:Animals; D002453:Cell Cycle; D002472:Cell Transformation, Viral; D004263:DNA Tumor Viruses / Q000235:genetics; D006801:Humans; D009857:Oncogenes