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Insulin and IGF‐1 regulate the expression of the pituitary tumor transforming gene (PTTG) in breast tumor cells
Author(s) -
Thompson Alvin D.,
Kakar Sham S.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.05.008
Subject(s) - ly294002 , insulin , cancer research , pi3k/akt/mtor pathway , transfection , protein kinase b , chemistry , medicine , mcf 7 , endocrinology , biology , gene expression , cell culture , microbiology and biotechnology , cancer cell , signal transduction , gene , cancer , biochemistry , genetics , human breast
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.