Anti-BIN3 monoclonal antibody, clone 4B5

Tamoxifen is the most commonly used drug to treat estrogen receptor positive (ER+) breast cancer. However, many patients with ER+ breast cancer have experienced resistance and other adverse side effects following treatment with tamoxifen. Furthermore, clinical and pathological parameters have thus far failed to predict the efficiency of tamoxifen administration. Therefore, gene signature based models for the prediction of survival time of such patients are urgently needed. In the current study, gene expression levels and follow-up information of samples from GSE17705 and GSE22219 databases were used to construct a risk score model based on Cox multivariate regression. The expression levels of 10 genes were included in the model: CCNB2, CCNA2, FOXD1, WSB2, RBPMS, CTDSP1, BIN3, SLBP, EPRS, FTO. The samples in the high-risk group had a relative early distant relapse time period (median survival time of 3.75 years) compared with the patients in the low risk group (median survival time of 6.5 years, P<0.01). For further validation, a further two independent datasets (GSE26971, GSE58644) were assessed. The overall survival time period of patients with high-risk scores in these datasets was significantly longer than those with low-risk scores (P<0.01). Furthermore, the associations between clinical parameters and risk score were investigated, and it was revealed that the risk score was significantly correlated with tumor age, tumor stage and grade. In addition, a 5-year survival nomogram was plotted in order to facilitate the utilization of risk score along with other clinical data. In summary, using the transcriptomic profile, a multi-gene expression based risk score was developed and was revealed as being able to successfully predict the outcome of patients with ER+ breast cancer treated with tamoxifen for 5 years.

Actin dynamics are necessary at multiple steps in the formation of multinucleated muscle cells. BAR domain proteins can regulate actin dynamics in several cell types, but have been little studied in skeletal muscle. Here, we identify novel functions for the N-BAR domain protein, Bridging integrator 3 (Bin3), during myogenesis in mice. Bin3 plays an important role in regulating myofiber size in vitro and in vivo. During early myogenesis, Bin3 promotes migration of differentiated muscle cells, where it colocalizes with F-actin in lamellipodia. In addition, Bin3 forms a complex with Rac1 and Cdc42, Rho GTPases involved in actin polymerization, which are known to be essential for myotube formation. Importantly, a Bin3-dependent pathway is a major regulator of Rac1 and Cdc42 activity in differentiated muscle cells. Overall, these data classify N-BAR domain proteins as novel regulators of actin-dependent processes in myogenesis, and further implicate BAR domain proteins in muscle growth and repair. (C) 2013 Elsevier Inc. All rights reserved.