Disease relevance of DSC2

• Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3 [1].
• Loss of Dsc2 (8/19) and de novo expression of Dsc1 (11/19) and Dsc3 (6/19) was also found in colorectal adenocarcinomas on a background of colitis [2].
• Two examples include the antimetastatic, tumor suppressor genes, desmocollin 3 (DSC3) and MASPIN, which are frequently silenced in this manner in human breast cancer [3].

High impact information on DSC2

• In contrast, daily intravenous injections of DG2 IgG given to mice had no effect on DLD-2 tumor growth but reduced growth of C6 tumors by approximately 30%--a statistically significant difference [4].
• Tumor cell proliferation was monitored after treatment with rHu-bFGF or the DG2 or DE6 IgG monoclonal antibody to rHu-bFGF in culture and in vivo [4].
• These data identify DSC2 mutations as a cause of ARVC in humans and demonstrate that physiologic levels of DSC2 are crucial for normal cardiac desmosome formation, early cardiac morphogenesis, and cardiac function [5].
• Morpholino knockdown in zebrafish embryos revealed a requirement for dsc2 in the establishment of the normal myocardial structure and function, with reduced desmosomal plaque area, loss of the desmosome extracellular electron-dense midlines, and associated myocardial contractility defects [5].
• Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2 [6].

Biological context of DSC2

• In contrast to MAb 1D11.16, which caused a dose-dependent decrease in RA synovial cell growth, MAb DG2 (up to 100 micrograms/ml) had no effect on cell growth [7].
• A 4 kb fragment of the desmocollin 3 promoter directs reporter gene expression to parakeratotic epidermis and primary hair follicles [8].

Anatomical context of DSC2

• Indirect immunofluorescence studies on COS-7 cells transiently transfected with desmocollin 1-3 cDNAs showed that the patient's serum contained IgG and IgA antibodies to desmocollin 3 as well as IgG antibodies to desmocollin 2 [9].
• DSC3 message was expressed before that of DSG3 in the dental and lingual epithelium where its spatial distribution matched that of DSG2, but after DSG3 in the non-glandular gastric epithelium [10].

Associations of DSC2 with chemical compounds

• METHODS: To isolate the effect of caffeine from that of other components of guarana, we adopted two different doses of whole extract (G1-0.130 g/kg; G2-0.325 g/kg) or decaffeinated extract (DG1, DG2) [11].
• In the absence of exogenous cytokines, the sponge-induced angiogenesis was profoundly suppressed by dexamethasone (5 micrograms/day), but not modified by IL-1ra, IL-8-AS, TNF-AB, and DG2 alone [12].

Analytical, diagnostic and therapeutic context of DSC2

• We elucidated the exon-intron structures of the DSC1 and DSC3 genes using PCR amplification of genomic DNA and direct sequencing of BAC clones [13].
• We have found switching between desmocollins in sporadic colorectal adenocarcinoma with a reduction in Dsc2 protein (in 8/16 samples analysed by immunohistochemistry) being accompanied by de novo expression of Dsc1 (16/16) and Dsc3 (7/16) [2].
• Gamma-camera imaging and distribution studies revealed that CEA-containing tumors selectively accumulate DG2 but Rec R does not [14].
• Monoclonal antibody D11-DG2 (DG2) against carcinoembryonic antigen (CEA) was examined for suitability for radioimmunodetection of human tumors grown in nude mice [14].

References