The expression and role of hybrid insulin/insulin-like growth factor receptor type 1 in endometrial carcinoma cells.
Insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF-IR) can assemble heteromerically as a hybrid insulin/IGF-I receptor (hybrid-R) in tissues that express both molecules. There is little information about hybrid-R in endometrial carcinoma, in which both IR and IGF-IR are frequently overexpressed. We used immunoprecipitation to detect hybrid-R expression in two endometrial carcinoma cell lines: HEC-1a, which has low estrogen receptor (ER) expression, and Ishikawa, which is positive for ER expression. To explore the role of hybrid-R in endometrial carcinoma cells, we examined phosphorylation of extracellular signal-regulated kinase (ERK1/2), which is a key molecule in the mitogen-activated protein kinase (MAPK) pathway. The effect of inhibiting IGF-I, IGF-II, and insulin on cell cycle progression and apoptosis was assessed by flow cytometry. Both cell lines expressed hybrid-R, and HEC-1a cells had higher expression levels than did Ishikawa cells. IGF-I induced ERK1/2 phosphorylation in HEC-1a cells mainly through hybrid-R; in Ishikawa cells, this effect was mediated only in part by hybrid-R. Insulin stimulated ERK1/2 phosphorylation partly through hybrid-R in HEC-1a cells, but not in Ishikawa cells. Both IGFs and insulin increased cellular DNA content in the S phase of the cell cycle in HEC-1a through hybrid-R. In contrast, in Ishikawa cells, only insulin enhanced DNA content in S phase through hybrid-R. Both IGFs and insulin significantly decreased apoptosis in HEC-1a cells through hybrid-R, and a similar but moderate effect was observed in Ishikawa cells. Hybrid-R, which is present in endometrial carcinoma cells, may have an important role in mediating IGF- and insulin-induced cell growth and in preventing apoptosis.
Zhang
Guo
G
Department of Gynecology, Peking University People's Hospital, No. 11 Xi-Zhi-Men South Street, Xi Cheng District, Beijing, China.
Li
Xiaoping
X
Zhang
Lili
L
Zhao
Lijun
L
Jiang
Jing
J
Wang
Jianliu
J
Wei
Lihui
L
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D011972:Receptor, Insulin / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology*
D007328:Insulin; D011993:Recombinant Fusion Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D048049:Extracellular Signal-Regulated MAP Kinases