title: The G protein estrogen receptor (GPER) is regulated by endothelin-1 mediated signaling in cancer cells.
abstract: Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor involved in many diseases, including certain cardiovascular disorders and cancer. As previous studies have shown that the G protein estrogen receptor (GPER) may regulate ET-1 dependent effects on the vascular system, we evaluated whether GPER could contribute to the effects elicited by ET-1 in breast cancer and hepatocarcinoma cells. Here, we demonstrate that ET-1 increases GPER expression through endothelin receptor A (ETAR) and endothelin receptor B (ETBR) along with the activation of PI3K/ERK/c-Fos/AP1 transduction pathway. In addition, we show that GPER is involved in important biological responses observed upon ET-1 exposure, as the migration of the aforementioned tumor cells and the formation of tube-like structures in human umbilical vein endothelial cells (HUVECs). Our data suggest that GPER may contribute to ET-1 action toward the progression of some types of tumor.
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bartella
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
authors.forename: Ernestina Marianna
authors.initials: EM
authors.lastname: De Francesco
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Perri
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
authors.forename: Rosita
authors.initials: R
authors.lastname: Curcio
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Dolce
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy. Electronic address: marcellomaggiolini@yahoo.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Vivacqua
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D018808:Transcription Factor AP-1
keywords: Cancer cells; Endothelin-1; GPER; Migration; Signal transduction