title: Low spinophilin expression enhances aggressive biological behavior of breast cancer.
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.
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
authors: Daniela
authors: D
authors: Schwarzenbacher
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
authors: Verena
authors: V
authors: Stiegelbauer
authors: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Austria.
authors: Alexander
authors: A
authors: Deutsch
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
authors: Anna Lena
authors: AL
authors: Ress
authors: Institute of Pathology, Medical University of Graz, Austria.
authors: Ariane
authors: A
authors: Aigelsreiter
authors: Institute of Pathology, Medical University of Graz, Austria.
authors: Silvia
authors: S
authors: Schauer
authors: Center for Medical Research, Medical University of Graz, Austria.
authors: Karin
authors: K
authors: Wagner
authors: Department of Therapeutic Radiology and Oncology, Medical University of Graz, Austria.
authors: Tanja
authors: T
authors: Langsenlehner
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
authors: Margit
authors: M
authors: Resel
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
authors: Armin
authors: A
authors: Gerger
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, TX, USA.
authors: Hui
authors: H
authors: Ling
authors: Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, TX, USA.
authors: Cristina
authors: C
authors: Ivan
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, TX, USA.|Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, TX, USA.
authors: George Adrian
authors: GA
authors: Calin
authors: Institute of Pathology, Medical University of Graz, Austria.
authors: Gerald
authors: G
authors: Hoefler
authors: Center for Medical Research, Medical University of Graz, Austria.
authors: Beate
authors: B
authors: Rinner
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, TX, USA.
authors: Martin
authors: M
authors: Pichler
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000099273:Neurabins
chemical_list: D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000099273:Neurabins
keywords: breast cancer; cellular growth; invasion; prognosis; tumor suppressor