Low spinophilin expression enhances aggressive biological behavior of breast cancer

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

The Functional Erythropoetin rs1617640 Gene Polymorphism does not Affect Life Expectancy of Patients with Peripheral Arterial Disease

Background: A common functional variant (c.-1306A>C, rs1617640) in the gene encoding erythropoietin (EPO) has been linked to expression of erythropoietin and markers of erythropoiesis. Aim of the current study was the analysis of the role of this polymorphism for long term survival of patients with peripheral arterial disease (PAD). Methods: EPO genotypes as well as biomarkers for erythropoiesis were analyzed in a cohort of 946 patients with PAD. Survival follow-up was performed 20 years af-ter recruitment of patients. Results: Twenty years after recruitment, 752 (79.5%) patients were dead, 103 (10.9%) were still alive, and 91 (9.6%) were lost-to-follow up. In a Cox regression analysis including smoking habit, sex, type-2 diabetes, hypercholesterolemia and arterial hypertension, EPO genotypes were not associated with overall survival (Hazard ratio 0.63; 95% confidence interval 0.88–1.08, p = 0.63). Conclusions: The functional EPO rs1617640 gene polymorphism, irrespective of its association with markers of erythropoiesis, does not affect survival of PAD patients

The Erythropoetin rs1617640 Gene Polymorphism Associates with Hemoglobin Levels, Hematocrit and Red Blood Cell Count in Patients with Peripheral Arterial Disease

Background: Erythropoietin has a pivotal role in erythropoiesis and angiogenesis. A common polymorphism (rs1617640, A &gt; C) in the promoter of the erythropoietin gene (EPO) has been associated with erythropoietin expression and microvascular complications of diabetes. We aimed to analyze the potential role of this polymorphism in the pathogenesis of peripheral arterial disease (PAD). Methods: EPO genotypes and laboratory markers for erythropoiesis were determined in 945 patients with PAD. Results: The minor EPO rs1617640 C-allele was associated in an allele-dose-dependent manner with hemoglobin levels (p = 0.006), hematocrit (p = 0.029), and red blood cell count (p = 0.003). In a multivariate linear regression analysis including conventional risk factors diabetes, sex, and smoking, EPO genotypes were furthermore associated with age at onset of PAD symptoms (p = 0.009). Conclusions: The EPO rs1617640 gene polymorphism affects erythropoiesis, leads to an earlier onset of PAD, and is a potential biomarker for the pathogenesis of this disease