title: Diacylglycerol kinase α mediates 17-β-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line through the G protein-coupled estrogen receptor GPR30.
abstract: Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (DGKs) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. DGK α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that DGK α activity is required for 17-β-estradiol (E2)-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line. Impairment of DGK α activity also influences basal cell proliferation and growth in soft agar of Hec-1A, while it has no effects on basal cell motility. Moreover, we show that DGK α activity induced by E2, as well as its observed effects, are mediated by the G protein-coupled estrogen receptor GPR30 (GPER). These findings suggest that DGK α may be a potential target in endometrial cancer therapy.
authors.affiliation: Department of Clinical and Experimental Medicine and Biotechnology Center for Applied Medical Research, University of Piemonte Orientale Amedeo Avogadro, Novara, Italy. nicoletta.filigheddu@med.unipmn.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Filigheddu
authors.forename: Sara
authors.initials: S
authors.lastname: Sampietro
authors.forename: Federica
authors.initials: F
authors.lastname: Chianale
authors.forename: Paolo E
authors.initials: PE
authors.lastname: Porporato
authors.forename: Miriam
authors.initials: M
authors.lastname: Gaggianesi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Gregnanin
authors.forename: Elena
authors.initials: E
authors.lastname: Rainero
authors.forename: Michele
authors.initials: M
authors.lastname: Ferrara
authors.forename: Beatrice
authors.initials: B
authors.lastname: Perego
authors.forename: Francesca
authors.initials: F
authors.lastname: Riboni
authors.forename: Gianluca
authors.initials: G
authors.lastname: Baldanzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Graziani
authors.forename: Nicola
authors.initials: N
authors.lastname: Surico
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D016889:Endometrial Neoplasms; D004789:Enzyme Activation; D057075:Enzyme Assays; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D052999:Quinazolinones / Q000494:pharmacology; D034622:RNA Interference; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: C109584:GPER1 protein, human; D010880:Piperidines; D052999:Quinazolinones; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C058544:R 59949; D004958:Estradiol; C480280:DAGLA protein, human; D008071:Lipoprotein Lipase