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Regulation of the proto-oncogenes bcl-2 and c-myc by the Wilms' tumor suppressor gene WT1
S M Hewitt1, S Hamada, T J McDonnell
1Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
The Wilms' tumor gene WT1 functions as a tumor suppressor gene, repressing transcription of several growth factors and growth factor receptors. The bcl-2 and c-myc proto-oncogenes are essential for regulation of apoptosis and cell proliferation with roles in development and oncogenesis. We found that WT1 can repress transcription of both the bcl-2 and c-myc promoters. This suggests that WT1 regulates bcl-2 and c-myc during renal development, and the loss of functional WT1 results in deregulation of bcl-2 and c-myc, contributing to tumor formation.
Insights
The Wilms' tumor gene (WT1) suppresses tumor growth by repressing key genes. Loss of WT1 function leads to the deregulation of bcl-2 and c-myc, promoting tumor formation.
Area of Science:
- Molecular Biology
- Oncology
- Developmental Biology
Background:
- The Wilms' tumor gene (WT1) is a known tumor suppressor.
- WT1 represses transcription of growth factors and receptors.
- Proto-oncogenes bcl-2 and c-myc are crucial for apoptosis and cell proliferation.
Purpose of the Study:
- To investigate the regulatory relationship between WT1, bcl-2, and c-myc.
- To understand WT1's role in renal development and oncogenesis through bcl-2 and c-myc regulation.
Main Methods:
- Analysis of WT1's effect on bcl-2 and c-myc promoter activity.
- Investigating gene regulation mechanisms in renal development.
Main Results:
- WT1 was found to repress the transcription of both bcl-2 and c-myc promoters.
- This repression indicates a direct regulatory role of WT1 on these proto-oncogenes.
Conclusions:
- WT1 plays a significant role in regulating bcl-2 and c-myc during kidney development.
- Disruption of WT1 function leads to dysregulation of bcl-2 and c-myc, contributing to Wilms' tumor development.