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: Daniela Schwarzenbacher, Verena Stiegelbauer, Alexander Deutsch, Anna Lena Ress, Ariane Aigelsreiter, Silvia Schauer, Karin Wagner, Tanja Langsenlehner, Margit Resel, Armin Gerger, Hui Ling, Cristina Ivan, George Adrian Calin, Gerald Hoefler, Beate Rinner, Martin Pichler
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 13 Pg. 11191-202 (May 10 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25857299 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Microfilament Proteins
• Nerve Tissue Proteins
• RNA, Messenger
• neurabin

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Breast Neoplasms (genetics, metabolism, mortality, pathology)
• Cell Movement
• Cell Proliferation
• Cell Transformation, Neoplastic
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoenzyme Techniques
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Microfilament Proteins (genetics, metabolism)
• Neoplasm Staging
• Nerve Tissue Proteins (genetics, metabolism)
• Prognosis
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays