title: Insulin-like factor binding protein-3 promotes the G1 cell cycle arrest in several cancer cell lines.
abstract: Insulin-like growth factor binding protein-3 (IGFBP-3) is a multi-functional protein known to induce apoptosis of various cancer cells in an insulin-like growth factor (IGF)-dependent and IGF-independent manner. In our previous study, we found that IGFBP-3 induced apoptosis through the activation of caspases in 786-O cells. In this study, we further examined that whether IGFBP-3 induced apoptosis through the induction of cell cycle arrest in 786-O, A549 and MCF-7 cells. Our results showed that overexpressed IGFBP-3 resulted in typical apoptotic ultrastructures in A549 cells under transmission electron microscope. The result of flow cytometry analysis indicated that IGFBP-3 arrested the cell cycle at G1-S phase in 786-O, A549 and MCF-7 cells. In A549 cells, quantitative real-time PCR and Western blot analysis showed a significant change in the expression of cell cycle-regulated proteins-a decrease in cyclin E1 expression, an increase in p21 expression. These results indicate a possible mechanism for G1 cell cycle arrest by IGFBP-3. Taken together, cyclin E1 and p21 may play important roles in the IGFBP-3-inducing G1 cell cycle arrest and apoptosis in several human cancer cells.
authors.affiliation: College of Life Sciences, Hebei University, Baoding, Hebei, 071002, PR China. dawnwuchen@163.com
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Liu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Huanna
authors.initials: H
authors.lastname: Tian
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Zhang
authors.forename: Fangming
authors.initials: F
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000378:metabolism*; D061986:MCF-7 Cells
chemical_list: D018797:Cell Cycle Proteins; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018972:Insulin-Like Growth Factor Binding Protein 3; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4