title: Insulin-like growth factor binding protein-3 is a new predictor of radiosensitivity on esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Luo
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Tian
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Medical Imaging and Interventional Center, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Jing-Xian
authors.initials: JX
authors.lastname: Shen
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Li-Ru
authors.initials: LR
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Qiao-Qiao
authors.initials: QQ
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Meng-Zhong
authors.initials: MZ
authors.lastname: Liu
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D000077277:Esophageal Squamous Cell Carcinoma; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011379:Prognosis; D034622:RNA Interference; D011836:Radiation Tolerance / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3