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Onco-suppressor genes and their involvement in cancer (review)
1Department of Biochemistry, University of Glasgow, Scotland.
Abstract:
Onco-suppressor genes are a heterogeneous set of genes that inhibit the cancer-related phenotype of cells. Because they are difficult to identify, only a few have been described. Evidence for their existence has mainly been indirect and comes from the following types of study. 1. Recessive cancer genes in higher and lower eukaryotes have been detected. If both alleles of these genes are deleted or inactivated, cancer develops. 2. Studies on cell hybrids have implicated genes which suppress various stages in the malignant conversion of normal cells e.g. immortalisation, morphological conversion and metastasis. 3. The isolation from virally induced transformants of flat, non-tumorigenic revertants in which expression of the transforming gene is not down-regulated suggests the presence of genes which suppress the effects of transformation. 4. Blocks to differentiation can be bypassed by inducing compounds or differentiation factors. 5. Studies on tumor inhibitory factors such as tumour necrosis factor and beta-TGF show that they have different effects on different types of cell-acting to promote growth in some cases and inhibit it in others. 6. The discovery of cis-acting negatice regulatory elements suggests that interaction of such elements with proteins may be important for control of gene expression particularly of infecting oncogenic viruses. 7. Suppression of the transformed phenotype of malignant cells by contact with normal cells that controls growth of neighboring cells. 8. The inhibition of proliferation of transformed cells by transfection with DNA from normal cells may be a useful method for cloning onco-suppressor genes. We discuss what is known and what is not known about this important class of gene.
Insights
Onco-suppressor genes inhibit cancer development but are hard to find. Research uses indirect evidence from cell studies, gene interactions, and tumor factors to understand these crucial cancer-fighting genes.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Onco-suppressor genes counteract cellular cancerous traits.
- Identifying these genes is challenging, with limited discoveries to date.
- Evidence for their function is primarily indirect.
Purpose of the Study:
- To review current knowledge on onco-suppressor genes.
- To discuss the indirect evidence supporting their existence and function.
- To highlight the challenges and future directions in onco-suppressor gene research.
Main Methods:
- Analysis of recessive cancer genes in eukaryotes.
- Cell hybrid studies to identify suppressors of malignancy.
- Isolation of non-tumorigenic revertants from viral transformants.
- Investigation of tumor inhibitory factors and regulatory elements.
- Studies on cell-cell contact inhibition and gene transfection.
Main Results:
- Recessive mutations in eukaryotes can lead to cancer.
- Cell hybrids reveal genes suppressing immortalization, morphological changes, and metastasis.
- Revertants indicate genes suppressing transformation effects.
- Tumor factors exhibit context-dependent growth effects.
- Negative regulatory elements and cell contact influence gene expression and proliferation.
Conclusions:
- Onco-suppressor genes play a vital role in preventing cancer.
- Diverse indirect methods provide evidence for their existence.
- Further research is needed to fully elucidate their mechanisms and identify specific genes.