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Updated: May 29, 2026
Experimental Metastasis Assay
Published on: August 24, 2010
Oncogenes and metastatic progression
A H Greenberg1, S E Egan, J A Wright
1Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Abstract:
It is now established that ras oncogenes can induce metastatic characteristics in primary diploid fibroblasts, nonsenescing fibroblasts and nonmetastasizing tumors. The issue of whether ras is directly involved in maintaining the metastatic phenotype through the expression and action of its gene product has been examined by analyzing the relationship to ras expression and to the production of the p21 ras-GTP complex, which is thought to mediate ras-transforming activity. While these expression and mutation studies support the idea that p21 ras directly regulates metastasis formation, it is also evident that there are many examples of human and murine cancers which show no differences in ras expression in primary and metastatic tumor cells. This may be partially explained by the ability of protein kinase-encoding oncogenes to also induce metastatic potential. In addition, the ability of ras to induce metastasis may be dependent on the regulation of its activity by other genes. Furthermore, transformation does not occur as an isolated genetic event, but is rather the result of interaction of two or more oncogenes. We suggest that the nature of these gene interactions will ultimately determine whether a cell is a benign transformant or a malignant and metastatic cancer.
Insights
Ras oncogenes can promote cancer metastasis, but their direct role is complex. Other oncogenes and gene interactions also significantly influence whether a cell becomes malignant and metastatic.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Ras oncogenes are known to induce metastatic characteristics in various cell types.
- The p21 ras-GTP complex is the presumed mediator of ras-driven transforming activity.
Purpose of the Study:
- To investigate the direct involvement of ras in maintaining the metastatic phenotype.
- To analyze the relationship between ras expression, p21 ras-GTP complex production, and metastasis.
Main Methods:
- Analysis of ras gene expression levels in primary and metastatic tumor cells.
- Examination of p21 ras-GTP complex formation.
- Review of existing literature on oncogene involvement in metastasis.
Main Results:
- While some studies support a direct role for p21 ras in metastasis, many cancers show no difference in ras expression between primary and metastatic cells.
- Protein kinase-encoding oncogenes can also induce metastatic potential.
- Ras's ability to induce metastasis may be regulated by other genes and oncogene interactions.
Conclusions:
- Ras oncogenes contribute to metastasis, but their role is not always direct or solely dependent on their own expression levels.
- The interplay between ras and other oncogenes, as well as regulatory gene networks, is crucial in determining cellular transformation and metastatic potential.
- Malignancy and metastasis arise from complex genetic interactions rather than isolated oncogenic events.
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