TY - JOUR
T1 - Low spinophilin expression enhances aggressive biological behavior of breast cancer
AU - Schwarzenbacher, Daniela
AU - Stiegelbauer, Verena
AU - Deutsch, Alexander
AU - Ress, Anna Lena
AU - Aigelsreiter, Ariane
AU - Schauer, Silvia
AU - Wagner, Karin
AU - Langsenlehner, Tanja
AU - Resel, Margit
AU - Gerger, Armin
AU - Ling, Hui
AU - Ivan, Cristina
AU - Calin, George Adrian
AU - Hoefler, Gerald
AU - Rinner, Beate
AU - Pichler, Martin
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Cellular growth
KW - Invasion
KW - Prognosis
KW - Tumor suppressor
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UR - http://www.scopus.com/inward/citedby.url?scp=84929649415&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.3586
DO - 10.18632/oncotarget.3586
M3 - Article
C2 - 25857299
AN - SCOPUS:84929649415
SN - 1949-2553
VL - 6
SP - 11191
EP - 11202
JO - Oncotarget
JF - Oncotarget
IS - 13
ER -