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Identification of cDNAs induced by the tumor suppressor Tsc2 gene using a conditional expression system in Tsc2
K Orimoto1, H Tsuchiya, J Sakurai
1Department of Experimental Pathology, Cancer Institute, Tokyo, Japan.
Abstract:
Alteration of the rat homologue of the tuberous sclerosis 2 (TSC2) gene is associated with dominantly inherited cancer in the Eker rat model, indicating a tumor suppressor nature. The ability of Tsc2 to activate signal transduction and transcription suggests that genes induced by Tsc2 may mediate its biological roles. Using a subtractive hybridization approach in combination with tetracycline operator systems, we identified a set of downstream genes affected by Tsc2. Regulated expression of wild-type Tsc2 gene in Eker renal carcinomas (RCs) resulted in marked expression of cell arrest or programmed cell-death-related genes and stress-induced genes. Thus, the data suggest that Tsc2 might contribute to regulation of the cell cycle and cell survival.
Insights
The tuberous sclerosis 2 (TSC2) gene acts as a tumor suppressor. Its activation in Eker rats influences cell cycle regulation and programmed cell death, suggesting a role in cancer development.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Alterations in the tuberous sclerosis 2 (TSC2) gene are linked to dominantly inherited cancers in the Eker rat model.
- The tumor suppressor function of TSC2 suggests its downstream targets mediate its biological roles.
Purpose of the Study:
- To identify downstream genes regulated by the TSC2 gene.
- To investigate the role of TSC2 in regulating cell cycle and cell survival in renal carcinomas.
Main Methods:
- Subtractive hybridization was employed to identify TSC2-affected genes.
- Tetracycline operator systems were used to regulate wild-type TSC2 gene expression in Eker renal carcinomas (RCs).
Main Results:
- A set of downstream genes regulated by TSC2 was identified.
- Expression of wild-type TSC2 in Eker RCs led to increased expression of genes associated with cell cycle arrest and programmed cell death.
- Stress-induced genes were also found to be upregulated.
Conclusions:
- TSC2 plays a role in the regulation of the cell cycle.
- TSC2 may contribute to the control of cell survival pathways.
- These findings elucidate potential mechanisms of tumor suppression by TSC2.