Low spinophilin expression enhances aggressive biological behavior of breast cancer.

// Daniela Schwarzenbacher 1,* , Verena Stiegelbauer 1,* , Alexander Deutsch 2,* , Anna Lena Ress 1 , Ariane Aigelsreiter 3 , Silvia Schauer 3 , Karin Wagner 4 , Tanja Langsenlehner 5 , Margit Resel 1 , Armin Gerger 1 , Hui Ling 6 , Cristina Ivan 7 , George Adrian Calin 6,7 , Gerald Hoefler 3 , Beate Rinner 4 and Martin Pichler 1,6 1 Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria 2 Division of Hematology, Department of Internal Medicine, Medical University of Graz, Austria 3 Institute of Pathology, Medical University of Graz, Austria 4 Center for Medical Research, Medical University of Graz, Austria 5 Department of Therapeutic Radiology and Oncology, Medical University of Graz, Austria 6 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, TX, USA 7 Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, TX, USA * These authors contributed euqally to this work Correspondence to: Martin Pichler, email: // Beate Rinner, email: // Keywords : breast cancer, tumor suppressor, prognosis, cellular growth, invasion Received : January 05, 2015 Accepted : February 19, 2015 Published : March 14, 2015 Abstract Spinophilin, a putative tumor suppressor gene, has been shown to be involved in the pathogenesis of certain types of cancer, but its role has never been systematically explored in breast cancer. In this study, we determined for the first time the expression pattern of spinophilin in human breast cancer molecular subtypes (n = 489) and correlated it with survival (n = 921). We stably reduced spinophilin expression in breast cancer cells and measured effects on cellular growth, apoptosis, anchorage-independent growth, migration, invasion and self-renewal capacity in vitro and metastases formation in vivo . Microarray profiling was used to determine the most abundantly expressed genes in spinophilin-silenced breast cancer cells. Spinophilin expression was significantly lower in basal-like breast cancer ( p <0.001) and an independent poor prognostic factor in breast cancer patients (hazard ratio = 1.93, 95% confidence interval: 1.24 -3.03; p = 0.004) A reduction of spinophilin levels increased cellular growth in breast cancer cells ( p <0.05), without influencing activation of apoptosis. Anchorage-independent growth, migration and self-renewal capacity in vitro and metastatic potential in vivo were also significantly increased in spinophilin-silenced cells ( p <0.05). Finally, we identified several differentially expressed genes in spinophilin-silenced cells. According to our data, low levels of spinophilin are associated with aggressive behavior of breast cancer.