Diacylglycerol kinase alpha mediates 17-beta-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line through the G protein-coupled estrogen receptor GPR30

作者：Filigheddu Nicoletta^*; Sampietro Sara; Chi****e Federica; Porporato Paolo E; Gaggianesi Miriam; Gregnanin Ilaria; Rainero Elena; Ferrara Michele; Perego Beatrice; Riboni Francesca; Baldanzi Gianluca; Graziani Andrea; Surico Nicola

来源：Cellular Signalling, 2011, 23(12): 1988-1996.

DOI：10.1016/j.cellsig.2011.07.009

• Diacylglycerol kinase
• Endometrial carcinoma
• Estrogen
• GPR30

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 alpha 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 alpha activity is required for 17-beta-estradiol (E2)-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line. Impairment of DGK 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 a 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 a may be a potential target in endometrial cancer therapy.

• 出版日期2011-12