Cellular oncogenes in neoplasia.
In recent years cellular homologues of many viral oncogenes have been identified. As these genes are partially homologous to viral oncogenes and are activated in some tumour cell lines they are termed "proto-oncogenes". In tumour cell lines proto-oncogenes are activated by either quantitative or qualitative changes in gene structure: activation of these genes was originally thought to be a necessary primary event in carcinogenesis, but activated cellular oncogenes, unlike viral oncogenes, do not transform normal cells in culture. In experimental models cooperation between two oncogenes can induce transformation of early passage cells, and this has become the basis of an hypothesis for multistep carcinogenesis. Proto-oncogene products also show sequence homology to various components in the mitogenic pathway (growth factors, growth factor receptors, signal transducing proteins and nuclear proteins), and it has been postulated that they may cause deregulation of the various components of this pathway. In human tumours single or multiple oncogene activation occurs. The pattern of oncogene activation in common solid malignancies is not consistent within any one class of tumour, nor is it uniform between classes, with three exceptions. In neuroblastoma, breast cancer, and perhaps in lung cancer there is relatively consistent activation of N-myc, neu, and c-myc/N-myc, respectively. Amplification of these genes generally correlates with poor prognosis. The introduction of methods for the direct study of oncogene transcription and their products will undoubtedly broaden our vision of cancer biology in man and, hopefully, add diagnostic and prognostic precision to tumour typing.
Chan
V T
VT
University of Oxford, Nuffield Department of Pathology, John Radcliffe Hospital, Oxford.
McGee
J O
JO
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D005260:Female; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D051381:Rats; D012190:Retroviridae / Q000235:genetics