Rabbit Anti-Human BRE (a.a. 94-383) Polyclonal antibody

Reelin is a secreted, signaling protein associated with neuronal cell positioning and migration. Recently, reelin was found to be epigenetically silenced in gastric and pancreatic cancers in which down-regulation was associated with increased migratory ability and reduced survival. Here we analyzed reelin expression by immunohistochemistry in 17 normal breast tissue samples from reduction mammoplasties and in two independent tissue microarrays of 136 and more than 2000 breast cancer biopsy samples, respectively. Results were analyzed with regard to clinical parameters, including BRE (Bloom, Richardson, Elston) grade, nodal status, estrogen receptor and HER2 status, and overall survival. Reelin was expressed in the luminal epithelium and myoepithelium of the normal human breast but not in cancerous breasts. Loss of reelin protein expression correlated significantly with decreased survival (P = 0.01) and positive lymph node status (P < 0.001). By measuring reelin expression and promoter methylation status in 39 primary breast tumors, as well as in breast cancer-derived cell lines before and after decitabine treatment, we established that reelin expression levels correlated inversely with promoter methylation status, whereas demethylation increased reelin mRNA expression in vitro. Reelin overexpression in MDA-MB231 cells, as well as incubation with recombinant reelin, suppressed cell migration, invadopodia formation, and invasiveness in vitro. We conclude that reelin may play an important role in controlling invasiveness and metastatic potential of breast cancer cells and that its expression is controlled by promoter methylation. (Am J Pathol 2010 177:2323-2333; DOI: 10.2353/ajpath.2010.100209)

Background: To maintain good health, it is important to eliminate extra reactive oxygen generated in the body. Furthermore, ingesting foods containing antioxidants is beneficial. The oxygen radical absorbance capacity (ORAC) values for black raspberry extract (BRE), blueberry extract (BBE), and raspberry extract (RBE) are 62, 66, and 49 mu M Trolox equivalents (TE)/g respectively. These values are higher than those for typical antioxidant foods that have been discovered so far ( 3-30 mu M TE/g). Our aim was to find new functionality from the food with the high ORAC value. Therefore, we have prepared these four berry extracts and examined whether they have anti-aging effects and if those effects correlate with their antioxidant activities. Methods: We studied the following effects of 4 berry extracts: 1) lens cell protective effects; 2) effects against alopecia; 3) induction of uncoupling protein-1 ( UCP1), a regulator of fat and energy consumption in adipocytes, and stimulation of irisin secretion from skeletal muscle cells; and 4) inhibitory effects on melanocyte tyrosinase activity. The evaluation method was based on below; 1) alpha-crystallin, type 17 collagen, heat shock protein 47 ( HSP47), UCP1 and Irisin mRNA by qRT-PCR, 2) the amount of the UCP1 and Irisin protein by ELISA. 3) Inhibition of tyrosinase activity was measured by dopachrome production using L-tyrosine. Results: In lens cells, alpha-crystallin mRNA expression was induced 1 hour after treatment of the cell with Blabina ( a powdered formulation containing BRE) and BRE. The extracts of all four berry species promoted the growth of follicle dermal papilla cells by 3-20% in a concentration-dependent manner. These berry extracts were also discovered to markedly induce the expression of mRNAs of type 17 collagen and HSP47 in the hair follicle stem cell and elevate the expression levels of UCP1 mRNA and its protein in adipocytes in a concentration-dependent manner. BRE and Blabina inhibited 5 alpha-reductase in follicle dermal papilla cells and tyrosinase activity in melanocytes at the concentrations which inhibited dopachrome production by at least 50%. Finally, Blabina was discovered to stimulate the irisin secretion from skeletal muscles. Conclusion: These results suggest that berry extracts, particularly BRE, have anti-aging effects through their higher antioxidant activities.