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The oncogene and its potential role in carcinogenesis
Abstract:
Cellular onc genes are a group of evolutionarily conserved sequences which are homologous to the transforming genes (v-onc) of oncogenic retroviruses. Although their functions in normal cells are largely not known, the sequence homology between viral and cellular onc genes is consistent with the idea that neoplastic transformation may, in some cases, be due to abnormal levels of cellular onc gene expression. Several models can be proposed for such a mechanism, including the insertion nearby of a viral promoter, alteration of the physiological promoter by a mutagenic agent, gene amplification, relocation in a transcriptionally active region of the genome as a consequence of chromosomal rearrangements and point mutations induced by external factors. Examples of these different mechanisms of onc gene activation can be found in animal and human tumors. Finally, the detail description of one cellular onc gene (c-sis), its relation to the viral gene and to a known cellular growth factor and its possible mode of activation in neoplastic transformation is presented.
Insights
Cellular oncogenes, homologous to viral oncogenes, may cause cancer through abnormal expression. Mechanisms include promoter insertion, mutation, amplification, or chromosomal rearrangements, as seen in tumors.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Cellular oncogenes share homology with viral oncogenes (v-onc).
- The precise functions of cellular oncogenes in normal cells remain largely unelucidated.
- Sequence homology suggests altered cellular oncogene expression can drive neoplastic transformation.
Purpose of the Study:
- To explore mechanisms by which cellular oncogenes may become abnormally expressed.
- To present examples of oncogene activation in animal and human tumors.
- To detail the cellular oncogene c-sis, its viral counterpart, and growth factor relation.
Main Methods:
- Comparative sequence analysis of viral and cellular oncogenes.
- Review of proposed models for oncogene activation.
- Case examples of oncogene activation in tumors.
- Detailed description of the c-sis oncogene.
Main Results:
- Several models for abnormal cellular oncogene expression were proposed.
- Mechanisms include viral promoter insertion, mutagenic alteration, gene amplification, chromosomal rearrangements, and point mutations.
- Examples of these activation mechanisms are documented in various tumors.
- The c-sis oncogene was described in relation to its viral homolog and a growth factor.
Conclusions:
- Abnormal expression of cellular oncogenes is a plausible mechanism for neoplastic transformation.
- Diverse genetic and epigenetic events can lead to oncogene activation.
- Understanding oncogene activation is crucial for cancer research and therapy.