期刊
ONCOTARGET
卷 6, 期 13, 页码 11191-11202出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3586
关键词
breast cancer; tumor suppressor; prognosis; cellular growth; invasion
资金
- Oesterreichische Nationalbank [14869]
- NIH/NCI [1UH2TR00943-01, 1 R01 CA182905-01]
- Laura and John Arnold Foundation
- RGK Foundation
- Estate of C. G. Johnson, Jr
- Erwin-Schroedinger Scholarship of the Austrian Science Funds [J3389-B23]
- Odyssey Program
- Estate of C. G. Johnson, Jr. at the University of Texas MD Anderson Cancer Center
- Austrian Science Fund (FWF) [J3389] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [J 3389] Funding Source: researchfish
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.
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