Growth factor genes as oncogenes.

The oncogenic retroviruses can be divided into two main categories: those that induce neoplasia after a long latent period (chronic leukemia viruses) and those that induce neoplasia relatively rapidly (acute transforming viruses). Chronic leukemia viruses do not transform cells in tissue culture and contain only the virally encoded genes. By nucleotide sequence comparison, it was possible to show that all retroviruses have a common evolutionary origin. In contrast, acute transforming viruses have substituted viral genes with genetic information specifically implicated in the oncogenic process. These genetic elements (oncogenes) were derived from uninfected host genomes. It was shown that one of the oncogenes, c-sis proto-oncogene, is the structural gene for the B-chain polypeptide of platelet-derived growth factor (PDGF). Furthermore, high level expression of human c-sis resulted in transformation of recipient cells. Similar results have been subsequently obtained for other growth factors, including granulocyte-macrophage colony stimulating factor, transforming growth factor alpha, epidermal growth factor, and basic fibroblast growth factor. It is possible that growth factor gene activation represents one of the steps leading toward malignancy in vivo.