Viruses, oncogenes, and cancer.

Our current theories of virus-induced cellular transformation have changed with the emerging recognition that all normal cells contain proto-oncogenes which convert to oncogenes and induce transformation when activated and/or amplified. Cellular oncogenes have been identified by homology to the transforming genes of acute retroviruses and by the transforming activity of tumor cell DNA in transfection assays. More than two dozen cellular oncogenes identified to date constitute a heterogeneous group of genes which are remarkably conserved among highly diverse species. Expression of proto-oncogenes is linked to normal growth and development; whereas their expression as oncogenes due to gene mutation, rearrangement, amplification or other processes leading to altered or overexpression is associated with the development of tumors. Functions of oncogene proteins are being identified. These include unique protein kinase activity, growth factor/growth factor receptor properties, and the presence of DNA-binding polypeptides. It also appears that cooperation between several activated cellular oncogenes may be required in the multistep process of oncogenesis. Our recent in vitro experimental evidence supports that human cell carcinogenesis is indeed a multistep process. In addition, the involvement of the activated cellular transforming genes met and H-ras in chemically induced human cell carcinogenesis has been shown. Advancement in molecular biology of oncogenes and their products is likely to result in improvements in cancer diagnosis and cancer therapy.