Insulin and IGF-1 regulate the expression of the pituitary tumor transforming gene (PTTG) in breast tumor cells.
The pituitary tumor transforming Gene (PTTG) is an oncogene that is highly expressed in most tumors analyzed to date. Here, we report the effects of insulin and the insulin like growth factor-1 (IGF-1) on the expression of PTTG. Using MCF-7 cells, a human breast cancer cell line, we observed that both insulin and IGF-1 upregulate the expression of PTTG mRNA by approximately 2.5-fold. Induction of PTTG mRNA expression by insulin or IGF-1 was completely blocked by the specific phosphatidylinositol (PI) 3 kinase inhibitor LY294002, but partially blocked by the MAP kinase inhibitor PD98059. Pretreatment of MCF-7 cells with actinomycin D completely blocked the stimulatory effect of insulin. Transfection of MCF-7 cells with a PTTG promoter-luciferase reporter construct revealed the dose-dependent stimulation of PTTG promoter activity by insulin, suggesting that the increase in PTTG expression by insulin is a result of activation of transcription of the PTTG gene. Taken together, our results suggest that insulin and IGF-1 regulate the expression of PTTG in MCF-7 cells primarily through the activation of PI3K/AKT cascade.
Thompson
Alvin D
AD
Department of Biochemistry and Molecular Biology, James Graham Brown Cancer Center, University of Louisville, 580 South Preston, Baxter II, 324, Kentucky 40202, USA.
Kakar
Sham S
SS
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009363:Neoplasm Proteins / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D064249:Securin; D013997:Time Factors
D007328:Insulin; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D007334:Insulin-Like Growth Factor I