Human Anti-Human CDH6 monoclonal Antibody, clone SFB957 [Biotin]

Cadherin superfamily genes play a role in a wide variety of developmental processes and mature functions of the vertebrate brain. In the present study, we mapped in situ the expression pattern of five classic cadherins (Cdh4, Cdh6, Cdh7, Cdh8, Cdh11) and eight delta-protocadherins (Pcdh1, Pcdh7, Pcdh8, Pcdh9, Pcdh10, Pcdh11, Pcdh17 and Pcdh19) in the primary somatosensory cortex of the adult mouse. All of these cadherins show layer-specific expression profiles in primary somatosensory cortex. Some cadherins (for example, Cdh4, Cdh7, Pcdh8) mark subsets of cells within a given lamina, while other cadherins (Cdh11 and Pcdh10) are expressed more widely in multiple layers. Results from tyramide-based double-fluorescence in situ hybridization (FISH) provide evidence that most single neurons express more than one cadherin in a combinatorial fashion in all layers of cerebral cortex. This combinatorial code is rather comprehensive because pairwise expression of cadherins can assume any type of combination (complementarity, partial or complete overlap, subset-specific expression, cell-size specific expression, etc.). We propose that the combinatorial expression of multiple cadherin genes contributes to the molecular specification of the vast complexity of neurons in cerebral cortex. (C) 2011 AGA Institute. Published by Elsevier Ltd. All rights reserved.

Cholangiocarcinoma (CC) is a raremalignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival of CC patients. Global genomic analyses identified a few recurrently mutated genes, some of them in genes involved in epigenetic patterning. In a previous study, we demonstrated global DNA methylation changes in CC, indicating major contribution of epigenetic alterations to cholangiocarcinogenesis. Here, we aimed at the identification and characterization of CC-related, differentially methylated regions (DMRs) in potential microRNA promoters and of genes targeted by identified microRNAs. Twenty-seven hypermethylated and 13 hypomethylated potential promoter regions of microRNAs, known to be associated with cancer-related pathways like Wnt, ErbB, and PI3K-Akt signaling, were identified. Selected DMRs were confirmed in 2 independent patient cohorts. Inverse correlation between promoter methylation and expression suggested miR-129-2 and members of the miR-200 family (miR-200a, miR-200b, and miR-429) as novel tumor suppressors and oncomiRs, respectively, in CC. Tumor suppressor genes deleted in liver cancer 1 (DLC1), F-box/WD-repeat-containing protein 7 (FBXW7), and cadherin-6 (CDH6) were identified as presumed targets in CC. Tissue microarrays of a representative and well-characterized cohort of biliary tract cancers (n=212) displayed stepwise downregulation of CDH6 and association with poor patient outcome. Ectopic expression of CDH6 on the other hand, delayed growth in the CC cell lines EGI-1 and TFK-1, together suggesting a tumor suppressive function of CDH6. Our work represents a valuable repository for the study of epigenetically altered miRNAs in cholangiocarcinogenesis and novel putative, CC-related tumor suppressive miRNAs and oncomiRs.