title: Assessment of insulin-like growth factor 1 receptor as an oncogene in esophageal squamous cell carcinoma and its potential implication in chemotherapy.
abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of multiple cancers. After ligand binding, IGF-1R can initiate the activation of the PI3K/AKT/mTOR and Ras/Raf/MEK/MAPK pathways to modulate cell proliferation, survival, differentiation, motility, invasion and angiogenesis. IGF-1R is a prerequisite for tumor progression and is one of the most attractive targets for therapeutic interventions in several types of cancer. In the present study, we determined the expression of IGF-1R in an esophageal squamous cell carcinoma (ESCC) cohort, investigated the detailed function of IGF-1R and screened the potential application of IGF-1R in the clinic. We verified the higher expression of IGF-1R in ESCC tumor tissues as compared to adjacent normal tissues. We also found that high expression of IGF-1R was associated with advanced tumor progression. We used ESCC cell lines and a mouse xenograft model to detect the function of IGF-1R in vitro and in vivo. Our results suggest the oncogenic function of IGF-1R in regulating cell proliferation, clonogenesis, the cell cycle and apoptosis. In addition, we found that IGF-1R was associated with the response to standard chemotherapy drugs 5-FU and cisplatin in an ESCC cell line. More importantly, we confirmed that the serum concentration of IGF-1/IGFBP3 can be used for predicting response to chemotherapy, and increased serum levels of IGF-1 and IGFBP-3 are associated with significantly higher rates of tumor response. In the present study, we demonstrated that IGF-1R is an important oncogene in ESCC and can be used to detect the chemotherapeutic response.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
authors.forename: Wang
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Ni
authors.initials: N
authors.lastname: Shi
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
authors.forename: Liuxing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
authors.forename: Shih Hsin
authors.initials: SH
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D009857:Oncogenes; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000187:drug effects / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1; D002945:Cisplatin; D005472:Fluorouracil