Anti-EPAS1 monoclonal antibody, clone 2H3

Surgery is the most effective treatment for breast cancer patients. However, some patients developed recurrence and distant metastasis after surgery. Adjuvant therapy is considered for high-risk patients depending on several prognostic markers, and lymphovascular invasion has become one of such prognostic markers that help physicians to identify the risk for distant metastasis and recurrence. However, the mechanism of lymphovascular invasion in breast cancer remains unknown. This study aims to unveil the genes and pathways that may involve in lymphovascular invasion in breast cancer. In total, 108 breast cancer samples were collected during surgery and microarray analysis was performed. Significance analysis of the microarrays and limma package for R were used to examine differentially expressed genes between lymphovascular invasion-positive and lymphovascular invasion-negative cases. Network and pathway analyses were mapped using the Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery. In total, 86 differentially expressed genes, including 37 downregulated genes and 49 upregulated genes were identified in lymphovascular invasion-positive patients. Among these genes, TNFSF11, IL6ST, and EPAS1 play important roles in cytokine-receptor interaction, which is the most enriched pathway related to lymphovascular invasion. Moreover, the results also suggested that an imbalance between extracellular matrix components and tumor micro-environment could induce lymphovascular invasion. Our study evaluated the underlying mechanisms of lymphovascular invasion, which may further help to assess the risk of breast cancer progression and identify potential targets of adjuvant treatment.

Obesity, which results from adipose differentiation and adipocyte hypertrophy, is a primary risk factor of these lifestyle-diseases. Obesity, is primary risk factor of these life-style-diseases, results from adipose differentiation and adipocyte hypertrophy. Adipose differentiation is regulated by several transcriptional factors, and we have focused here on the roles played by endothelial PAS domain protein 1 (EPAS1) in adipogenesis. EPAS1 was identified as a factor responsible for hypoxia responses, such as angiogenesis, here we demonstrated that EPAS1 is highly induced during adipose differentiation in vivo and in vitro. We then analyzed EPAS1 promoter activity during adipose differentiation in 3T3-L1 cells. We showed that the sequence -478/-445 is responsible for the up-regulation of EPAS1 expression during adipose differentiation and that the activity of this region is controlled by Sp1 and Sp3. To examine whether EPAS1 exerts an influence on adipogenesis, we overexpressed dominant negative form of EPAS1 in 3T3-L1 cells. The expression of EPAS1 (1-485) allowed cells to accumulate only a minimum amount of lipid droplets. Therefore, induction of EPAS1 expression is necessary for execution of adipose differentiation program. The mechanism involves the direct transcriptional regulation of Glut1, Glut4 and IRS3 genes by EPAS1. These results also confirmed that the protein level of EPAS1 was increased by insulin stimulation in adipocytes. Taken together, this result also indicated that EPAS1 plays a role in the part of insulin action. Therefore, these results suggest that the quantitative and functional alteration of EPAS1 are involved in metabolic syndrome occurrence.