Insulin-like growth factor binding protein-3 is a new predictor of radiosensitivity on esophageal squamous cell carcinoma
| Autor: | Shi Liang Liu, Ying Xue Wang, Meng Zhong Liu, Mian Xi, Li Ru He, Qiao Qiao Li, Li Ling Luo, Xiao Peng Tian, Lei Zhao, Jing Xian Shen, Peng Zhang, Dan Xie |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Esophageal Neoplasms Cell Survival medicine.medical_treatment Gene Expression Cell Cycle Proteins Models Biological Radiation Tolerance Insulin-like growth factor-binding protein Article Downregulation and upregulation Internal medicine Cell Line Tumor medicine Animals Humans Radiosensitivity Gene Silencing Phosphorylation Multidisciplinary biology Growth factor Cyclin-dependent kinase 2 Retinoblastoma protein Cell cycle Prognosis G1 Phase Cell Cycle Checkpoints Xenograft Model Antitumor Assays Cyclin E1 Disease Models Animal Endocrinology Insulin-Like Growth Factor Binding Protein 3 Gene Knockdown Techniques Cancer research biology.protein Carcinoma Squamous Cell RNA Interference Esophageal Squamous Cell Carcinoma |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep17336 |
| Popis: | Insulin-like growth factor binding protein-3 (IGFBP-3) plays an essential role in radiosensitivity of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism is not completely understood. Here, we observed that IGFBP-3 had favorable impact on the tumorigenicity of ESCC cells in nude mice by using an in vivo imaging system (IVIS) to monitor tumor growth treated with ionizing radiation (IR). Downregulation of IGFBP-3 expression enhanced tumor growth, inhibited anti-proliferative and apoptotic activity and result in IR resistance in vivo. Cell cycle antibody array suggested that silencing IGFBP-3 promoted transition from G0/G1 to S phase, perhaps though influencing Smad3 dephosphorylation and retinoblastoma protein (Rb) phosphorylation. Downregulation of P21 and P27 and upregulation of p-P27 (phospho-Thr187), cyclin-dependent kinase 2 (CDK2) and cyclin E1 might contribute to the G0/G1 to S phase transition promoted by IGFBP-3. Our results suggest that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in this IGFBP-3 mediated radiosensitivity transition in ESCC. |
| Databáze: | OpenAIRE |
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