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Viruses, oncogenes, and cancer
1Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Abstract:
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.
Insights
Normal cells contain proto-oncogenes that can become oncogenes, driving cellular transformation and tumor development. Understanding oncogene activation is key to advancing cancer diagnosis and therapy.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Normal cells possess proto-oncogenes crucial for growth and development.
- Proto-oncogenes can transform into oncogenes through activation or amplification, leading to cellular changes.
- Cellular oncogenes are conserved across species and identified through retroviral gene homology and transfection assays.
Purpose of the Study:
- To explore the role of proto-oncogenes and oncogenes in cellular transformation and carcinogenesis.
- To investigate the mechanisms of oncogene activation and their association with tumor development.
- To highlight the potential of oncogene research in improving cancer diagnosis and therapy.
Main Methods:
- Identification of cellular oncogenes via homology to viral transforming genes.
- Transfection assays using tumor cell DNA to detect transforming activity.
- In vitro experimental evidence to support multistep carcinogenesis models.
Main Results:
- Over two dozen cellular oncogenes identified, exhibiting conserved properties.
- Proto-oncogene expression linked to normal development; oncogene expression linked to tumors.
- Evidence supports a multistep process in human cell carcinogenesis, involving activated oncogenes like met and H-ras.
Conclusions:
- Oncogene activation, mutation, or amplification is associated with tumor formation.
- Cooperation between multiple oncogenes may be essential for oncogenesis.
- Advances in oncogene molecular biology promise improved cancer diagnostics and therapeutics.