Identification of cDNAs induced by the tumor suppressor Tsc2 gene using a conditional expression system in Tsc2 mutant (Eker) rat renal carcinoma cells.

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.