title: IGF-1 activates the P13K/AKT signaling pathway via upregulation of secretory             clusterin.
abstract: Secretory clusterin (sCLU) is a type of stress-induced, pro-survival glycoprotein             elevated in early-stage cancer. It enhances cancer cell survival and is associated             with several types of cancer progression. In this study, we measured the PI3K/AKT             signaling activity by determining the phosphorylation level of the AKT protein,             namely pAKT. A549 human non-small cell lung carcinoma (NSCLC) cells were treated             with insulin-like growth factor-1 (IGF-1) for various periods of time. The results             showed that IGF-1 activated the PI3K/AKT signaling pathway in the A549 cells in             a time-dependent manner. Western blot analysis was performed to determine the             expression of sCLU protein in A549 cells treated with IGF-1. IGF-1 elevated the             expression of sCLU. To determine whether sCLU is required for the IGF-1 activation             of the PI3K/AKT signaling pathway, the A549 cells were treated with IGF-1 and             sCLU antisense oligonuleotide (sCLU ASO). sCLU ASO blocked the IGF-1 activation             of the PI3K/AKT signaling pathway. These results demonstrate that IGF-1 activates             the P13K/AKT signaling pathway via the upregulation of sCLU. The present study             implies that this pathway may uncover a new mechanism for cancer progression and             reveal new targets for drug development in the treatment of NSCLC.
authors.affiliation: Department of Radiation Oncology, Renji Hospital, Shanghai Jiao                     Tong University School of Medicine, Shanghai 200120, P.R. China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Ma
authors.forename: Yongrui
authors.initials: Y
authors.lastname: Bai
mesh_terms: D045744:Cell Line, Tumor; D051152:Clusterin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D051152:Clusterin; D016376:Oligonucleotides, Antisense; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt