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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin (delta-cells), and pancreatic polypeptide (PP-cells) in a sequential order. The endocrine cells are believed to arise from a stem cell with neuronal traits. The developmental lineage from a common neuron-like progenitor is evidenced by: transient coexpression of more than one cell type-specific hormone in immature cells, expression of neuronal markers during islet cell development, and the pluripotentiality of clones of insulinoma cells to develop into cells expressing other islet cell hormones. The four mature endocrine cell types assume a particular organization within the islets of Langerhans in a process where cell adhesion molecules are involved. In this study we have analyzed the expression of neural cell adhesion molecule (NCAM) and cadherin molecules in neonatal, young, and adult rat islet cells as well as in glucagonomas and insulinomas derived from a pluripotent rat islet cell tumor. Whereas primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons. The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N-cadherin in brain. Insulinoma cells express E-cadherin but differ from primary islet cells by expressing a second cadherin molecule, which is similar to N-cadherin. The expression of NCAM and cadherin isoforms in the glucagonoma suggest that this transformed alpha-cell type has converted to an immature phenotype with strong neuronal traits, reflecting the early palce of glucagon-producing cells in the islet cell lineage. In contrast, insulinoma cells are more islet-like in their phenotype and show less neuronal traits.
Mol Endocrinol 1992 Aug
PMID:Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas. 140 10

p120cas is a tyrosine kinase substrate implicated in ligand-induced receptor signaling through the epidermal growth factor, platelet-derived growth factor, and colony-stimulating factor receptors and in cell transformation by Src. Here we report that p120 associates with a complex containing E-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Furthermore, p120 precisely colocalizes with E-cadherin and catenins in vivo in both normal and Src-transformed MDCK cells. Unlike beta-catenin and plakoglobin, p120 has at least four isoforms which are differentially expressed in a variety of cell types, suggesting novel means of modulating cadherin activities in cells. In Src-transformed MDCK cells, p120, beta-catenin, and plakoglobin were heavily phosphorylated on tyrosine, but the physical associations between these proteins were not disrupted. Association of p120 with the cadherin machinery indicates that both Src and receptor tyrosine kinases cross talk with proteins important for cadherin-mediated cell adhesion. These results also strongly suggest a role for p120 in cell adhesion.
Mol Cell Biol 1994 Dec
PMID:Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes. 752 56

Simple epithelial cells are polygonal in shape, polarized in an apical-basal orientation, and organized into closely adherent sheets, characteristics that result from a variety of cellular specializations and adhesive proteins. These characteristics are lost when the epithelia transform during embryogenesis into mesenchymal cells or after neoplasia into invasive carcinoma cells. Of the syndecan family of transmembrane heparan sulfate proteoglycans, simple epithelia produce predominantly syndecan-1, which is found at basolateral surfaces and within adhesive junctions. To elucidate the function of this syndecan-1, normal murine mammary gland epithelia were made deficient in syndecan-1 by transfection with an expression vector containing the syndecan-1 cDNA in the antisense configuration. Several independently derived clones of stable transfectants contained the antisense cDNA in their genome and expressed the antisense transcript. These grew either as epithelial islands of closely adherent polygonal cells, identical to both the parental cells and the vector-only control transfectants, or as individual elongated fusiform cells that invaded and migrated within collagen gels, like mesenchymal cells, but were anchorage-independent for growth. The clones that retained epithelial characteristics were moderately deficient in cell surface syndecan-1 (greater than 48% of control levels) but did not differ from control cells in expression of beta 1-integrins and E-cadherin, or in F-actin organization. However, the clones of fusiform cells were severely deficient in cell surface syndecan-1 (less than 12% of control levels) and showed rearranged beta 1-integrins, markedly reduced E-cadherin expression, and disorganized F-actin filaments, but retained mammary epithelial markers. Therefore, depleting epithelia of cell surface syndecan-1 alters cell morphology and organization, the arrangement and expression of adhesion molecules, and anchorage-dependent growth controls. Thus, cell surface syndecan-1 is required to maintain the normal phenotype of simple epithelia.
Mol Biol Cell 1995 May
PMID:Loss of cell surface syndecan-1 causes epithelia to transform into anchorage-independent mesenchyme-like cells. 754 31

The tyrosine kinase substrate p120cas (CAS), which is structurally similar to the cell adhesion proteins beta-catenin and plakoglobin, was recently shown to associate with the E-cadherin-catenin cell adhesion complex. beta-catenin, plakoglobin, and CAS all have an Arm domain that consists of 10 to 13 repeats of a 42-amino-acid motif originally described in the Drosophila Armadillo protein. To determine if the association of CAS with the cadherin cell adhesion machinery is similar to that of beta-catenin and plakoglobin, we examined the CAS-cadherin-catenin interactions in a number of cell lines and in the yeast two-hybrid system. In the prostate carcinoma cell line PC3, CAS associated normally with cadherin complexes despite the specific absence of alpha-catenin in these cells. However, in the colon carcinoma cell line SW480, which has negligible E-cadherin expression, CAS did not associate with beta-catenin, plakoglobin, or alpha-catenin, suggesting that E-cadherin is the protein which bridges CAS to the rest of the complex. In addition, CAS did not associate with the adenomatous polyposis coli (APC) tumor suppressor protein in any of the cell lines analyzed. Interestingly, expression of the various CAS isoforms was quite heterogeneous in these tumor cell lines, and in the colon carcinoma cell line HCT116, which expresses normal levels of E-cadherin and the catenins, the CAS1 isoforms were completely absent. By using the yeast two-hybrid system, we confirmed the direct interaction between CAS and E-cadherin and determined that CAS Arm repeats 1 to 10 are necessary and sufficient for this interaction. Hence, like beta-catenin and plakoglobin, CAS interacts directly with E-cadherin in vivo; however, unlike beta-catenin and plakoglobin, CAS does not interact with APC or alpha-catenin.
Mol Cell Biol 1995 Sep
PMID:The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. 765 99

Cadherins are discussed not in terms of their adhesive function but rather as morphoregulatory proteins. Changes in gene expression following cadherin transfection of cells in culture or by overexpression in embryos have, until now, not been reported. We established a protocol for stable transfection of Xenopus XTC cells and generated cells bearing high levels of membrane-integrated mouse uvomorulin (E-cadherin) or Xenopus XB-cadherin. These cell lines showed drastically impaired substrate adhesion on fibronectin and laminin. In immunoblot and radioimmunoprecipitation experiments, we found that fibronectin and alpha 3/beta 1 integrin are downregulated. The reduced amounts of proteins result from a decrease of the respective mRNAs as proven by RNase protection assays. Coprecipitations revealed that transfected cadherin molecules are complexed with alpha-catenin and beta-catenin at plasma membranes. However, the alpha-catenin present in the XB-cadherin complex differs immunologically from that found in the uvomorulin complex. When a truncated form of XB-cadherin lacking 38 of the most C-terminal amino acids was expressed in XTC cells, complex formation with endogenous catenins was abolished. In these transfectants, substrate adhesion was not affected. These results prove that complex formation of transfected cadherins in XTC cells with endogenous beta-catenin correlates with altered synthesis of certain substrate adhesion molecules.
Mol Cell Biol 1995 Sep
PMID:Cadherin transfection of Xenopus XTC cells downregulates expression of substrate adhesion molecules. 765 25

Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer. This mechanism is frequently associated with the impairment of either E-cadherin expression or function. However, mechanisms of such abnormalities have not been fully elucidated. In this study, we demonstrated that the function of E-cadherin was completely abolished in the human gastric cancer cell line HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins, beta-catenin. Although immunofluorescence staining of HSC-39 cells by using an anti-E-cadherin antibody (HECD-1) revealed the strong and uniform expression of E-cadherin on the cell surface, cell compaction and cell aggregation were not observed in this cell. Western blotting (immunoblotting) using HECD-1 exhibited a 120-kDa band which is equivalent to normal E-cadherin. Northern (RNA) blotting demonstrated a 4.7-kb band, the same as mature E-cadherin mRNA. Immunoprecipitation of metabolically labeled proteins with HECD-1 revealed three bands corresponding to E-cadherin, alpha-catenin, and gamma-catenin and a 79-kDa band which was apparently smaller than that of normal beta-catenin, indicating truncated beta-catenin. The 79-kDa band was immunologically identified as beta-catenin by using immunoblotting with anti-beta-catenin antibodies. Examination of beta-catenin mRNA by the reverse transcriptase-PCR method revealed a transcript which was shorter than that of normal beta-catenin. The sequencing of PCR product for beta-catenin confirmed deletion in 321 bases from nucleotides +82 to +402. Southern blotting of beta-catenin DNA disclosed mutation at the genomic level. Expression vectors of Beta-catenin were introduced into HSC-39 cells by transfection. In the obtained transfectants, E-cadherin-dependent cell-cell adhesiveness was recovered, as revealed by cell compaction, cell aggregation, and immunoflourescence staining. From these results, it was concluded that in HSC-39 cells, impaired cell-cell adhesion is due to mutations in beta-catenin which results in the dysfunction of E-cadherin.
Mol Cell Biol 1995 Mar
PMID:Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39. 786 12

We constructed cDNA libraries from a clonal human teratocarcinoma-derived cell line and two retinoic acid-induced derivatives: a homogeneous population of neurons and a FACS-isolated, non-neuronal population. These libraries are large and representative of the cells from which they were derived, as determined by colony hybridization. PCR analysis indicates that the transcripts encoding P- and E-cadherin are down-regulated whereas the the prion protein (PrP) transcript is up-regulated in neurons. These cells offer a promising system for investigations of human prion infection and the cDNA libraries provide a source of neuron-specific genes.
Brain Res Mol Brain Res 1994 Aug
PMID:Gene regulation during neuronal and non-neuronal differentiation of NTERA2 human teratocarcinoma-derived stem cells. 798 43

E-cadherin is a Ca(2+)-dependent cell adhesion molecule involved in cell-cell interaction. In its normal physiological function it plays an important role in embryonic development and tissue morphogenesis. Recent studies have shown that in cancer development E-cadherin can act as a suppressor of invasion. Indeed, in several kinds of carcinomas allelic loss of the E-cadherin/Uvomorulin locus and decreased E-cadherin expression have been described. The importance of E-cadherin in human cancer development may be substantiated by molecular analysis of the E-cadherin transcript. Therefore, we isolated and characterized the human E-cadherin cDNA. Comparison of the nucleotide and deduced amino acid sequences revealed that the human E-cadherin is highly homologous to the mouse E-cadherin (uvomorulin) and to other members of the cadherin family.
Mol Biol Rep 1993 Feb
PMID:Molecular cloning and characterization of the human E-cadherin cDNA. 845 5

A genomic clone containing the 5' region of the mouse P-cadherin gene has been isolated from Balb/c mice. A major feature of this genomic sequence is the presence of a first intron (Il), 215 bp long, located 48 bp downstream of the translation start ATG codon. The presence of Il has been detected both in Balb/c and C57BL/6 mouse strains, being located at the same position with respect to coding sequences as in the mouse E-cadherin and chicken L-CAM genes. The transcription initiation site of the mouse P-cadherin gene has been located at about 68 nt from the ATG start codon, giving an estimation for the size of the first exon of the mouse P-cadherin gene of 116 bp. The sequence of the 5' upstream region of the P-cadherin gene presents structural similarities with the recently described 5' region of the mouse E-cadherin gene: absence of a TATA box, presence of a CAAT box at -65, two putative AP2-binding motifs, at -101 and +31, and a GC-rich region containing a potential SP1-binding element at -88. However, no sequence homologous to the palindromic sequence, E-pal, found on the E-cadherin promoter has been found in the 5' region of the P-cadherin gene. These results indicate that, in contrast to a previous report, the mouse E and P-cadherin genes exhibit a similar genomic organization both containing 15 introns and a similar size for the first two exons.
J Mol Biol 1993 Jun 05
PMID:The 5' flanking sequences of the mouse P-cadherin gene. Homologies to 5' sequences of the E-cadherin gene and identification of a first 215 base-pair intron. 851 62

A polymerase chain reaction strategy was utilized to identify members of the cadherin family of cell adhesion molecules that are expressed in normal human colon and colon carcinoma. E-cadherin (an epithelial cadherin) and OB-cadherin (a mesenchymal cadherin) were found to be present in the colon specimens. Furthermore, a novel semiquantitative polymerase chain reaction (PCR) assay was developed for each of these two cadherins. These assays were used to determine the relative levels of E-cadherin and OB-cadherin in normal human colon and colon carcinoma specimens. E-cadherin levels were found to be reduced approximately twofold in the adenocarcinoma specimens in comparison to matched normal colon specimens. In contrast, OB-cadherin levels did not correlate with malignant transformation. We speculate that this novel PCR method will be widely applicable for assessing E-cadherin mRNA levels in carcinomas.
Exp Mol Pathol 1995 Apr
PMID:E-cadherin and OB-cadherin mRNA levels in normal human colon and colon carcinoma. 854 95


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