title: Insulin-like growth factor 1 regulates growth of endometrial carcinoma through PI3k signaling pathway in insulin-resistant type 2 diabetes.
abstract: Previous studies have shown that insulin-like growth factor 1 (IGF-1) may be responsible for the higher risk for developing endometrial carcinoma (EMC) in insulin-resistant type 2 diabetes mellitus (T2DM) patients. However, the underlying mechanisms are not understood. Here, we compared T2DM patients with or without EMC. We did not find difference in the serum levels of IGF-1, insulin-like growth factor 2 (IGF-2), IGF-1 binding protein 3, as well as the activation of IGF-1 receptor (IGF1R) in endometrial cells between T2DM patients with or without EMC. However, the levels of IGF2R activation and activation of PI3k, an IGF1R downstream factor, were significantly higher in endometrial cells in T2DM patients with EMC. In vitro analyses of activation of IGF1R, IGF2R, PI3k and CCND1 in EMC cells or IGF2R-overexpressing EMC cells by IGF-1 or IGF-2 suggest that increases in IGF2R in endometrial cells in T2DM may increase PI3k/CCND1-dependent cell growth through loss of competitive binding of IGF-2 to IGF1R, as a possible explanation for the higher risk for developing EMC in T2DM.
authors.affiliation: Hebei Medical UniversityShijiazhuang 050051, China; Department of Gynaecology, Hebei General HospitalShijiazhuang 050051, China.
authors.forename: Congwei
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Gynaecology, Hebei General Hospital Shijiazhuang 050051, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Hebei Medical UniversityShijiazhuang 050051, China; Department of Endocrinology, Hebei General HospitalShijiazhuang 050051, China.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Gynaecology, Hebei General Hospital Shijiazhuang 050051, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, Hebei General Hospital Shijiazhuang 050051, China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Ning
keywords: Cyclin D1 (CCND1); Insulin-like growth factor 1 (IGF-1); endometrial carcinoma (EMC); insulin-like growth factor 1 receptor (IGF1R); insulin-like growth factor 2 (IGF-2); insulin-like growth factor 2 receptor (IGF2R); phosphatidylinositol-3 kinase (PI3k); type 2 diabetes mellitus (T2DM)