GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growthin vitroandin vivo

• DOI: 10.18632/oncotarget.4241
• Publication Date: 2015-09-15T06:28:55Z
• Authors: Adele Chimento; Rosa Sirianni; Ivan Casaburi; Fabiana Zolea; Pietro Rizza; Paola Avena; Rocco Malivindi; Arianna De Luca; Carmela Campana; Emilia Martire; Francesco Domanico; Francesco Fallo; Giulia Carpinelli; Lidia Cerquetti; Donatella Amendola; Antonio Stigliano; Vincenzo Pezzi
• Keywords: GPER; Fulvestrant

We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use tamoxifen, a selective modulator (SERM), appears effective in reducing ACC growth vitro vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on G protein-coupled (GPER). Aim this study was to investigate effect non-steroidal GPER G-1 modulating cell growth. found is able exert inhibitory H295R cells and, xenograft model, Treatment with induced cycle arrest, DNA damage death activation intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing specific shRNA partially reversed G-1-mediated inhibition without affecting ERK data suggest existence activated GPER-independent effects remain be clarified. In conclusion, provides rational further mechanism action order include drug treatment option limited therapy ACC.