Avian oncogenes

This chapter begins with an outline of the cell cycle and the importance of normal transcriptional factors and proto-oncogenes, emphasising those characterised in avian species (almost entirely from the domestic fowl). The different classes of avian oncogene are then described, together with their relationship to proto-oncogenes. 

Two avian oncogenes that encode protein kinases are cytoplasmic proteins not associated with membranes rel and mil rel occurs in avian reticuloen-dotheliosis virus (REV-T), which has been described as the most virulent of all retroviruses, causing a rapidly fatal lymphoma with a latent period of one to two weeks and a mortality approaching 100% (Moore Bose, 1989). A modified form of REV has... 

Infection by viruses carrying oncogenes can cause malignant cell growth. Although first recognized as causative agents in avian cancers 90 years ago, for much of the twentieth century there was doubt that any human cancers were initiated in this way. Even now, almost all the information in this area refers to nonhuman animals, which presents a number of problems. First, as was already... 

Frykberg, L., S. Palmieri, H. Beug, T. Graf, M.J. Hayman, and B. Vennstrom, Transforming capacities of avian erythroblastosis virus mutants deleted in the erbA or erbB oncogenes. Cell, 1983. 32(1) 227-38. 

Vennstrom B, Bishop JM. Isolation and characterization of chicken DNA homologous to the two putative oncogenes of avian erythroblastosis virus. Cell 1982 28 135-143. 

Retroviruses have featured prominently in recent advances in the molecular understanding of cancer. Most retroviruses do not kill their host cells but remain integrated in the cellular DNA, replicating when the cell divides. Some retroviruses, classified as RNA tumor viruses, contain an oncogene that can cause the cell to grow abnormally (see Fig. 12-47). The first retrovirus of this type to be studied was the Rous sarcoma virus (also called avian sarcoma virus Fig. 26-31), named for F. Peyton Rous, who studied chicken tumors now known to be caused by this virus. Since the initial discovery of oncogenes by Flarold Varmus and Michael Bishop, many dozens of such genes have been found in retroviruses. 

The c-Ski oncogene is a phosphoprotein originally isolated from chicken as the cellular homologue of v-ski carried by the Sloan-Kettering avian retrovirus... 

Li, Y., Turck, C.M., Teumer, J.K., and Stavnezer, E. 1986. Unique sequence, ski, in Sloan-Kettering avian retroviruses with properties of a new cell-derived oncogene. J. Virol. 57 1065-1072. 

In fact, when the primary structure of the first steroid receptor, the human glucocorticoid receptor [79] was deduced from the nucleotide sequence the homology of this central region with the product of the v-erb-A oncogene of the avian erythroblastosis virus immediately became conspicuous [80]. This similarity subsequently led to the identification of c-erb-A, the cellular counterpart of v-erb-A, as the gene for a thyroid hormone receptor [92,93]. The kinship amongst these sequences has also greatly helped to identify cDNA clones for other steroid hormone receptors. 

Fig. 4. A diagrammatic comparison of the structures of the human c-fms protein, the human PDGF receptor and the v-kit oncogene of the avian virus HZ4. Solid dots represent the position of cysteine residues in the extracellular domains of the proteins.

Acute transforming retroviruses are a unique subset of retroviruses that have acquired the ability to produce cancer in rodents and avian species in a relatively short time period (several weeks). Examples of acute transforming retroviruses include the Rous sarcoma virus (RSV), which produces sarcomas in chickens, and the Harvey murine sarcoma virus (Ha-MSV), which produces sarcomas in rats and mice. Studies utilizing RSV provided the first evidence that cellular genes, now termed oncogenes, exist in vertebrate cells. 

Crk is a protooncogene, related to v-crk, the oncogene of the avian sarcoma virus CTIO. Crk is the abbreviation of T regulator of ase. Although, Crk induces tyrosine phosphorylation, it is not a tyrosine kinase. It is actually a linker, containing SH2 and SH3 domains which links up with tyrosine kinases. 

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