DNA tumor viruses have been isolated from six different virus families (Table 4.2). These repre- sent a diverse set of viruses with differing structures, cell tropisms, genome organizations, and
aThese cumbersome but still widely used designations of viral oncoproteins contain basic structural data. p stands for protein, gp stands for glycoprotein, and pp stands for phospho- protein; the latter is not applied consistently but, instead, is used mainly in conjunction with the src product. The numbers stand for estimated molecular weight in kilodaltons, and the superscript lists the genes from which the coding information is derived in 5′ to 3′ direction. In this chapter, we simply use the abbreviation of the oncogene; however, we use roman letters, with the first letter capitalized, to indicate the oncoprotein. Relevant contributions of viral genes to the oncoprotein are mentioned in the text.
bTransducing retrovirus with two oncogenes.
cfps and fes are the same oncogene derived from the avian and feline genomes, respectively.
draf and mil are the same oncogene derived from the murine and avian genomes, respectively.
Figure 4.7 Examples of transducing retroviruses that are replication defective. Oncogenes are shaded. Top line represents RSV, which is replication competent and carries an intact gag, pol, and env gene. In contrast, each of the other retroviruses is missing at least some portion of the three essential replication genes. In their place is the oncogene. (MC29) avian myelocytomatosis virus (myc oncogene); (Ha-MSV) Harvey murine sarcoma virus (ras oncogene); (Mo-MSV) Moloney murine sarcoma virus (mos oncogene); (Ab-MLV) Abelson murine leukemia virus (abl oncogene); (SSV) simian sarcoma virus (sis oncogene). (Adapted from Coffin et al., 1997, with permission of authors and publisher.)
Figure 4.8 Example of proviral insertional mutagenesis or cis-activation. Activation of the c-myc proto- oncogene by ALV integration. The c-myc proto-oncogene has three exons. Exon 1 does not encode protein. In lymphomas, the most common integration site for ALV is in the first intron of the c-myc gene. Subse- quently a deletion occurs that removes the first exon of c-myc and the 5′ portion of the provirus. Transcrip- tion from the 3′ LTR then leads to higher than normal levels of c-myc protein expression. (Adapted from Cooper, 1995, with permission of author and publisher.)
replication strategies. There is compelling evidence that some DNA tumor viruses can cause cancer in humans (Chapter 12). Others do not pose a cancer threat to humans, but cause cancer in animal hosts or transform cells in culture. Some important if not revolutionary insights have come from the study of DNA tumor viruses, such as adenovirus and SV40, which cause cancer only in experimental settings. The discovery of tumor suppressor genes (Chapter 5) was greatly facilitated by the study of the two aforementioned viruses in a manner similar to the way the study of retroviruses led to our understanding of cellular oncogenes and their functions. Tumor suppressor proteins function to prevent the cell from becoming cancerous, in that inactivation of all copies of a tumor suppressor gene or protein places a cell at an increased risk for cancer development. In this case, loss of gene function means increased cancer risk. This is in contrast to the oncogenes. Proto-oncogenes carry out a role in the normal functioning of a cell. Mutations within proto-oncogenes that result in gain of function can lead to the development of cancer (Chapter 5).