ONCOGENES OF DNA AND RNA TUMOR-VIRUSES AND THE ORIGIN OF CELLULAR ONCOGENES

Oncogenes were first described as the genes of DNA tumor viruses responsible for in vivo and in vitro neoplastic transformation induced by such viruses. The first oncogenes described were the oncogenes of polyoma, SV40 and papilloma viruses. The polyoma virus oncogene has been designated the 'middle' T (tumor) antigen, whereas the SV40 oncogene is designated the 'large' T antigen. The large T of the polyoma virus can also be considered an oncogene, because it is capable of 'immortalizing', but not transforming primary cell cultures. Other oncogenes of DNA tumor viruses are the EIA of adenoviruses and the E7 gene of papilloma viruses. It has been proposed that some of the oncogenes of DNA tumor viruses act by binding the products of tumor suppressor genes, such as the retinoblastoma gene product Rb. In general, the products of the oncogenes of DNA tumor viruses need the cooperation of other oncogenes to establish a completely transformed phenotype. Oncogenes have been discovered in all replication defective RNA tumor viruses, whereas they are not present in the genomes of replication competent RNA tumor viruses, which can also give rise to a neoplastic phenotype, in vivo, but by a different mechanism. The discovery of oncogenes in RNA tumor viruses has led to the concept that these oncogenes are actually present in the genomes of all eucaryotic organisms and have been transduced and, in some cases, modified by a retrovirus. The characterization of the oncogenes of acute transforming retroviruses has led to the present classification of oncogenes, which include genes coding for proteins having different functional properties, but all characterized by having some role in the pathway which regulates cell proliferation. The experimental approach of DNA transfection has led to the discoveries of some oncogenes already known from the genomes of retroviruses and also of some new oncogenes which had never been transduced by retroviruses. The knowledge derived from retrovirus research and from the use of the DNA transfection technique has opened a whole new field of science thereby contributing greatly to our understanding of the mechanisms underlying neoplastic transformation and also to the understanding of normal cell physiology.