Transforming Genes of Retroviruses and Cancer Cells
An approach towards understanding mechanisms involved in processes leading to malignancy has come from studies of acute transforming retroviruses. These viruses have arisen in nature by recombination of replication-competent type C RNA viruses with a limited set of evolutionarily well-conserved cellular genes. When incorporated within the retrovirus genome, such transduced cellular (onc) sequences acquire transforming properties. To investigate the role of onc-related genes in human cancer, we have utilized molecular cloning techniques to isolate the human cellular homologues of a number of retroviral on£ genes. These genes are often actively transcribed in human tumor cells, and in some cases in normal cells as well. We have mapped the chromosomal locations of onc-related genes in human cells and shown that in some cases such genes are involved in highly specific translocations associated with certain cancers. These findings raise the possibility that such translocations may affect onc gene expression in a manner that contributes to the neoplastic process. By a different approach involving DNA-mediated gene transfer techniques, dominant transforming genes, or oncogenes, have been detected in human tumors and tumor cell lines. The role of these genes in the malignant process remains to be elucidated. However, many of the oncogenes so far detected are related to the onc genes of bas, has, or kis, a small family of retroviruses comprised of BALB, Harvey, and Kirsten murine sarcoma viruses, respectively.