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Search for metastasis suppressor genes
1Laboratory of Pathology, National Cancer Institute, Bethesda, Md.
Abstract:
Cell fusion experiments have predicted the existence of cancer metastasis suppressor genes. The E1a gene of Adenovirus 2 has been demonstrated to suppress c-Ha-ras induction of experimental metastatic potential in rat embryo fibroblasts. Another approach to the identification of candidate metastasis suppressor genes has utilized differential or subtraction hybridizations to clone genes which are downregulated as cells become highly metastatic. To date, three such genes have been identified: nm23, WDNM1, and fibronectin. With regard to nm23, downregulation of nm23 RNA levels in high metastatic potential cells has been demonstrated in a wide variety of rodent metastasis systems, including K-1735 murine melanoma cell lines, nitrosomethylurea-induced rat mammary tumors, MMTV-induced mouse mammary tumors, and ras +/- E1a transfected rat embryo fibroblasts. Whether the expression of the nm23 gene, and other down-regulated genes in tumor metastasis, correlates with changes in metastatic potential, or actually has suppressive activity, will require transfection experiments.
Insights
Researchers are identifying cancer metastasis suppressor genes using cell fusion and gene cloning techniques. The nm23 gene is frequently downregulated in highly metastatic cells, suggesting its role in suppressing tumor spread.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cell fusion experiments suggest the existence of metastasis suppressor genes.
- The Adenovirus 2 E1a gene can suppress experimental metastatic potential induced by c-Ha-ras.
- Identifying genes downregulated during metastasis is a key strategy.
Purpose of the Study:
- To review methods for identifying cancer metastasis suppressor genes.
- To highlight candidate genes such as nm23, WDNM1, and fibronectin.
- To discuss the observed downregulation of nm23 in metastatic cells.
Main Methods:
- Cell fusion experiments.
- Differential and subtraction hybridization techniques for gene cloning.
- Analysis of gene expression levels in various metastatic cell models.
Main Results:
- Adenovirus 2 E1a gene suppresses experimental metastatic potential.
- Three candidate metastasis suppressor genes (nm23, WDNM1, fibronectin) identified via subtractive hybridization.
- Downregulation of nm23 RNA levels observed across diverse rodent metastasis models.
Conclusions:
- nm23, WDNM1, and fibronectin are candidate metastasis suppressor genes.
- Consistent downregulation of nm23 in high metastatic potential cells across multiple systems.
- Further transfection experiments are needed to confirm the suppressive activity of nm23 and other downregulated genes in tumor metastasis.