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.
Orimoto
K
K
Department of Experimental Pathology, Cancer Institute, Tokyo, Japan.
Tsuchiya
H
H
Sakurai
J
J
Nishizawa
M
M
Hino
O
O
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism; D007700:Kinetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics; D014402:Tuberous Sclerosis / Q000235:genetics; D000077005:Tuberous Sclerosis Complex 2 Protein; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D012333:RNA, Messenger; D012097:Repressor Proteins; C000624653:TSC2 protein, human; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins