Chapter 13 : Under the Influence: from the Provirus Hypothesis to Multistep Carcinogenesis

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A part of a first group at University of California at San Francisco (UCSF) worked on the early events in retrovirus replication that result in the establishment of a provirus. Another part worked on aspects of proviral gene expression, especially mechanisms, such as ribosomal frameshifting, that permit synthesis of the viral enzymes required for forming a provirus. Yet another portion of the group studied the oncogenic consequences of proviral integration, including insertional activation and the capture of host proto-oncogenes. All of these components, arrayed around a schematic drawing of a provirus, revealed the depth of commitment to Teminism. The idea that insertional activation of proto-oncogenes might constitute the first step in a cancerous process initiated by retroviruses lacking viral oncogenes took flight with the demonstration that avian leukosis viruses augment expression of the c- proto-oncogene by nearby integration of its provirus. These findings stimulated similar work with the mouse mammary tumor virus (MMTV), resulting in the discovery of the gene, the first cloned member of a large gene family known to govern early developmental events in diverse organisms. In the studies the first group has moved beyond the study of MMTV proviruses as insertional mutagens to consider more broadly the multistep nature of mammary carcinogenesis in hopes of understanding the genetic and physiological events that produce premalignant lesions, primary cancers, and metastases in human beings as well as mice.

Citation: Varmus H. 1995. Under the Influence: from the Provirus Hypothesis to Multistep Carcinogenesis, p 185-188. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch13
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1. Donehower, L. A.,, L. A. Godley,, C. M. Aldaz,, R. Pyle,, Y.-P. Shi,, D. Pinkel,, J. Gray,, A. Bradley,, D. Medina,, and H. E. Varmus. Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. Genes Dev., in press.
2. Donehower, L. A.,, M. Harvey,, B. L. Slagle,, M. J. McArthur,, C. A. Montgomery, Jr.,, J. S. Butel,, and A. Bradley. 1992. Mice deficient for p53 are developmental normal but susceptible to spontaneous tumours. Nature (London) 356: 215 221.
3. Hayward, W. S.,, B. G. Neel,, and S. M. Astrin. 1981. Activation of a cellular one gene by promoter insertion in ALV-induced lymphoid leukosis. Nature (London) 209: 475 479.
4. Kwan, H.,, V. Pecenka,, A. Tsukamoto,, T. G. Parslow,, R. Guzman,, T.-P. Lin,, W. J. Muller,, F. S. Lee,, P. Leder,, and H. E. Varmus. 1992. Transgenes expressing the Wnt-1 and int-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice. Mol. Cell. Biol. 12: 147 154.
5. Nusse, R.,, and H. E. Varmus. 1982. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31: 99.
6. Nusse, R.,, and H. E. Varmus. 1992. Wnt genes. Cell 69: 1073 1088.
7. Shackleford, G. M.,, C. A. MacArthur,, H. C. Kwan,, and H. E. Varmus. 1993. Mouse mammary tumor virus infection accelerates mammary carcinogenesis in Wnt-1 transgenic mice by insertional activation of int-2/ Fgf-3 and hst/Fgf-4. Proc. Natl. Acad. Sci. USA 90: 740 744.
8. Tsukamoto, A. S.,, R. Grosschedl,, R. C. Guzman,, T. Parslow,, and H. E. Varmus. 1988. Expression of the INT-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 55: 619 625.
9. Varmus, H. E. 1982. Form and function of retroviral proviruses. Science 216: 812.

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