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Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis
Published on: March 31, 2015
Complementation tagging of cooperating oncogenes in knockout mice
1Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract:
Gene disruption and overexpression in mice can be combined with proviral tagging to investigate the biochemical pathways in which oncogenes act. The phenomenon of oncogene collaboration permits a focussed genetic approach analogous to the strategies employed in suppressor screens in invertebrates and yeast. We illustrate here its application to investigating the action of the pim kinases in tumorigenesis. However, it should be possible to utilize this strategy for dissecting a much wider range of biochemical pathways in mammalian systems.
Insights
Investigating oncogene collaboration in mice using gene disruption and proviral tagging reveals insights into pim kinase pathways in tumorigenesis. This genetic approach can dissect broader mammalian biochemical pathways.
Area of Science:
- Mammalian genetics
- Cancer biology
- Molecular oncology
Background:
- Oncogenes play critical roles in tumorigenesis.
- Understanding oncogene function requires dissecting their biochemical pathways.
- Genetic strategies in model organisms offer powerful tools for biological discovery.
Purpose of the Study:
- To demonstrate a genetic strategy for investigating oncogene action in mammalian systems.
- To apply this strategy to understand the role of pim kinases in tumorigenesis.
- To highlight the potential of oncogene collaboration for dissecting broader biochemical pathways.
Main Methods:
- Combining gene disruption and overexpression in mice.
- Utilizing proviral tagging for genetic analysis.
- Employing the concept of oncogene collaboration for focused genetic studies.
Main Results:
- Successfully applied the strategy to investigate pim kinases in tumorigenesis.
- Demonstrated the utility of oncogene collaboration for genetic approaches.
- Provided a framework for dissecting diverse biochemical pathways in mammals.
Conclusions:
- Gene disruption, overexpression, and proviral tagging in mice provide a powerful method to study oncogene biochemical pathways.
- Oncogene collaboration enables focused genetic studies analogous to suppressor screens.
- This strategy is applicable to a wide range of biochemical pathways in mammalian systems, particularly in cancer research.
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