Disease relevance of Cdh3

• Although P-cadherin mutant mice have no apparent defect in epithelial cell adhesion, the desmoglein 3 mutant phenotype resembles that of patients with the autoimmune disease pemphigus vulgaris, in that the mice develop spontaneous mucous membrane blisters and trauma-induced skin blisters [1].
• This more pronounced differentiation was not seen for all tissues, however, as structures with a simple neural tube-like morphology were never found in teratomas lacking both N- and P-cadherin and organoid-like structures were rare in Ncad-/-tissue [2].
• However, complete absence of P-cadherin was observed in the fibroblast-like cells (CarB and CarC) and in spindle cell carcinomas [3].
• The P-cadherin mutant mice develop hyperplasia and dysplasia of the mammary epithelium with age [4].
• Alterations in P-cadherin expression were also detected in the p53 null papillomas: aberrant suprabasal localization and heterogeneous distribution were observed more frequently than in heterozygous and wild-type p53 papillomas [5].

High impact information on Cdh3

• E- or P-cadherin was transfected into L cells, which normally have little cadherin activity, and cellular aggregation of the resulting transfectants was observed to be a function of the cadherin molecule expressed [6].
• The interaction between nephrin and Neph1 is specific and not shared by either protein with P-cadherin, another integral slit diaphragm protein [7].
• BC44 mammary epithelial cells in culture, display phenotypic characteristics of basal epithelium, i.e., express basal cytokeratins 5 and 14 and P-cadherin, but no smooth muscle markers [8].
• In contrast to E- and N-cadherin- deficient mice, mice homozygous for the P-cadherin mutation are viable [4].
• Furthermore, the loss of P-cadherin from the myoepithelium has uncovered a novel function for this tissue in maintaining the undifferentiated state of the underlying secretory epithelium [4].

Biological context of Cdh3

• A computer search of the amino acid sequence homology of P-cadherin against itself showed that this molecule contains internal repeats in the extracellular domain [9].
• Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. I. Lung epithelial morphogenesis [10].
• A coincident upregulation of P-cadherin was observed in this area [11].
• Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR [12].
• This gene was also similar to the other in that the second intron, which corresponds to the P-cadherin first intron, is exceptionally longer than other introns [13].

Anatomical context of Cdh3

• In this study, we identified a novel class of cadherin, termed P-cadherin, using a visceral endoderm cell line PSA5-E [14].
• P-Cadherin first appeared in developing mouse embryos in the extraembryonic ectoderm and the visceral endoderm at the egg cylinder stage and later was expressed in various tissues [14].
• The expression of P-cadherin was transient in many tissues, and its permanent expression was limited to certain tissues such as the epidermis, the mesothelium, and the corneal endothelium [14].
• All epithelial cells of the lung express both E- and P-cadherin at the early developmental stage [10].
• Expression and the role of E- and P-cadherin in the histogenesis of the surface epidermis and hair follicles were examined using the upper lip skin of the mouse [15].

Associations of Cdh3 with chemical compounds

• The data demonstrate that integrin-mediated cell interaction with extracellular matrix is directly implicated in the control of P-cadherin expression, and that EGF and cell-extracellular matrix adhesion events are important regulators of the basal mammary epithelial cell phenotype [16].
• The amount of P-cadherin transcript was 2- to 4-fold higher in cells plated on the function-blocking anti-integrin antibodies and on the extracellular matrix proteins, as compared to cells plated on poly-L-lysine, whereas the K14 transcript levels were not significantly modified in response to adhesion [16].
• We tested whether the expression of P-cadherin, a molecule known to be located at the slit diaphragm, was altered by diabetes in vivo and by high glucose in vitro [17].

Regulatory relationships of Cdh3

• N-cadherin is expressed in the inner layer and P-cadherin in the outer layer of the ciliary epithelium [18].
• In the tooth germ at the late bell stage when the cells of the inner enamel epithelium began to polarize to differentiate into ameloblasts, the polarizing ameloblasts lost P-cadherin and strongly expressed E-cadherin [19].

Other interactions of Cdh3

• The proximal tubule progenitors express cadherin-6, the distal tubule cells express E-cadherin, whereas the glomeruli express P-cadherin [20].
• 5. N-cadherin expression persists in the inner layer as it develops into neural retina, but is turned off in the outer layer where the cells differentiate into retinal pigment epithelial (RPE) cells and express P-cadherin [18].
• We analyzed the subcellular distribution of beta-catenin in the cap-stage enamel organ and compared it with the expression of E- and P-cadherin by using confocal laser microscopy [11].
• Postnatal lethality of P-cadherin/desmoglein 3 double knockout mice: demonstration of a cooperative effect of these cell adhesion molecules in tissue homeostasis of stratified squamous epithelia [1].
• In parallel with our observations for NCAM, expression of P-cadherin was also apparently decreased by T3 (100 nM) [21].

Analytical, diagnostic and therapeutic context of Cdh3

• E/P-cadherin, alpha-catenin, ZO-1 and vinculin were localized with reference to AF in these cells using laser scan microscopy as well as conventional light and electron microscopy [22].
• From this we conclude that the apparent decrease in P-cadherin induced by 100 nM T3 and detected on Western blots reflects loss of gonocytes [21].
• Northern blot analysis of testicular RNA indicates the presence of N-Cad [4.3 and 3.5 kilobases (kb)] and P-Cad (3.5 kb) transcripts [23].
• Immunofluorescence analysis in 3D2.26 cell cultures showed loss of cortical actin filaments and destabilization of adherens junctions mediated by E- and P-cadherin, although both cadherin mRNAs were expressed in the transfectants [24].
• In this study using indirect immunofluorescence microscopy, we analyzed the distribution of two kinds of cadherins, E- and P-cadherin, in developing tooth germs [19].

References