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: Nicoletta Filigheddu, Sara Sampietro, Federica Chianale, Paolo E Porporato, Miriam Gaggianesi, Ilaria Gregnanin, Elena Rainero, Michele Ferrara, Beatrice Perego, Francesca Riboni, Gianluca Baldanzi, Andrea Graziani, Nicola Surico
• Journal: Cellular signalling (Cell Signal) Vol. 23 Issue 12 Pg. 1988-96 (Dec 2011) ISSN: 1873-3913 [Electronic] England
• PMID: 21802511 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• GPER1 protein, human
• Piperidines
• Quinazolinones
• Receptors, Estrogen
• Receptors, G-Protein-Coupled
• R 59949
• Estradiol
• DAGLA protein, human
• Lipoprotein Lipase

Topics

• Cell Adhesion
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival
• Endometrial Neoplasms
• Enzyme Activation
• Enzyme Assays
• Estradiol (pharmacology)
• Female
• Gene Knockdown Techniques
• Humans
• Lipoprotein Lipase (antagonists & inhibitors, genetics, metabolism)
• Piperidines (pharmacology)
• Quinazolinones (pharmacology)
• RNA Interference
• Receptors, Estrogen
• Receptors, G-Protein-Coupled (genetics, metabolism)