ABSTRACT
PURPOSE: The aim of this study was to clarify DNA methylation profiles determining the clinicopathological diversity of urothelial carcinomas. METHODS: Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation450 BeadChip in 46 paired samples of non-cancerous urothelium (N) and corresponding cancerous tissue (T), and 26 samples of normal control urothelium obtained from patients without urothelial carcinomas (C). For genes of interest, correlation between DNA methylation and mRNA expression was examined using the Cancer Genome Atlas database. In addition, the role of a selected target for cancer-relevant endpoints was further examined in urothelial carcinoma cell lines. RESULTS: The genes showing significant differences in DNA methylation levels between papillary carcinomas and more aggressive non-papillary (nodular) carcinomas were accumulated in signaling pathways participating in cell adhesion and cytoskeletal remodeling. Five hundred ninety-six methylation sites showed differences in DNA methylation levels between papillary and nodular carcinomas. Of those sites, that were located in CpG-islands around transcription start site, 5'-untranslated region or 1st exon, 16 genes exhibited inverse correlations between DNA methylation and mRNA expression levels. Among the latter, only the KLF11 gene showed papillary T sample-specific DNA hypermethylation in comparison to C and N samples. The DNA methylation levels of KLF11 were not significantly different between T samples and N samples or T samples and C samples for patients with papillo-nodular or nodular carcinomas. Knockdown experiments using the urothelial carcinoma cell lines HT1376 and 5637, which are considered models for papillary carcinoma, revealed that KLF11 participates in altering the adhesiveness of cells to laminin-coated dishes, although cell growth was not affected. CONCLUSION: These data indicate that DNA hypermethylation of KLF11 may participate in the generation of papillary urothelial carcinomas through induction of aberrant cancer cell adhesion to the basement membrane.
Subject(s)
Carcinoma, Papillary , Cell Adhesion , DNA Methylation , Urinary Bladder Neoplasms , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Cell Adhesion/genetics , Cell Line, Tumor , CpG Islands/genetics , DNA Methylation/genetics , Gene Expression Regulation, Neoplastic , Repressor Proteins/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Urothelium/pathology , Urothelium/metabolismSubject(s)
Adenocarcinoma , Colonic Neoplasms , Ganglioneuroma , Adenocarcinoma/complications , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Ganglioneuroma/diagnosis , Ganglioneuroma/diagnostic imaging , HumansABSTRACT
The effect of monomer sequence along the network chain on the swelling behavior of polymer gels should be clarified for the advanced control of swelling properties of gel materials. To this end, we systematically investigated the swelling properties of poly(acrylamide derivative) gels with the same composition but different monomer sequence by utilizing two gel synthetic methods: copolymerization giving a random network and co-crosslinking giving a blocky network. Both of the copolymerization and the co-crosslinking gels were prepared from the combination of two of the three following monomers: hydrophilic N,N-dimethylacrylamide (DMAAm), hydrophobic N-n-butylacrylamide (NBAAm), and thermoresponsive N-isopropylacrylamide (NIPAAm) with various monomer compositions. The swelling measurement of the obtained gels showed totally different behaviors between the copolymerization and the co-crosslinking gels, even with the same monomer composition. The copolymerization gels had the average property from the two monomers, depending on monomer composition, because random monomer distribution changed the affinity of each network chain to water. On the other hand, the co-crosslinking gels behaved as if two components independently contributed to the swelling properties, probably due to the domain structure derived from two kinds of prepolymers.
ABSTRACT
The initial determination of left-right asymmetry is an essential process in embryonic development. In mouse embryo, cilia in the node play an important role generating the nodal flow that subsequently triggers left-right determination in the embryo. Although nodal cilia have historically been thought to have a 9 + 0 axonemal configuration, the existence of 9 + 2 cilia has been reported so far. Because the distribution of those two types of cilia within the node has not yet been reported, we assessed the arrangement of 9 + 0 and 9 + 2 cilia in the node. In this study, we concluded that most of the nodal cilia were 9 + 0 in structure and there were much fewer 9 + 2 cilia than 9 + 0 cilia. Furthermore, the two types of cilia were randomly distributed in the node with no regularity. In addition, we studied the embryonic origin of the crown cells surrounding the node to better understand their identity.
