title: Insulin promotes proliferation, survival, and invasion in endometrial carcinoma by activating the MEK/ERK pathway.
abstract: The involvement of insulin in endometrial carcinoma (EC) was investigated using radioimmunoassay, Western blot, immunoprecipitation, MTT, and Annexin V-FITC/PI assays in tissue samples and cultured cells. Serum levels of insulin, p-p52Shc, p-p46Shc, Shc·Grb2 complexes, p-MEK, p-ERK, and cyclin D1 were elevated in patients with EC. Expression of key proteins in the MEK/ERK pathway, including p-p52Shc, Shc·Grb2 complexes, p-MEK, p-ERK, and cyclin D1, was significantly higher in patients with advanced FIGO stage, high grade, and lymph-node metastasis and correlated positively with serum insulin concentration. Insulin promotes Ishikawa 3-H-12 cell proliferation, survival, and invasion, and these effects induced by insulin were significantly blocked by MEK inhibitor PD98059. Insulin thus promotes EC cell proliferation, survival, and invasion via the MEK/ERK pathway.
authors.affiliation: Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuanxi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lizhi
authors.initials: L
authors.lastname: Zhang
authors.forename: Wenyan
authors.initials: W
authors.lastname: Tian
authors.forename: Shaofang
authors.initials: S
authors.lastname: Hua
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xue
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness
chemical_list: D007328:Insulin; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases