Disease relevance of MUC1

• In concert with these results, we show that MUC1 stimulates ERalpha-mediated transcription and contributes to E2-mediated growth and survival of breast cancer cells [1].
• The MUC1 protein is aberrantly overexpressed by most human breast carcinomas [1].
• Increased MUC1 immunoreactivity was observed in most adenocarcinomas of the breast, lung, stomach, pancreas, prostate, and ovary [2].
• The univariate analysis showed that tumor size, intrahepatic metastasis, lymph node metastasis, MUC4 expression, and MUC1 expression were statistically significant risk factors affecting the outcome of the patients with ICC-MF [3].
• Epithelial ovarian cancers expressed several mucins including MUC1, 2, 4, and 5AC; MUC3 and 5B were rarely expressed [4].
• These findings indicate that overexpression of MUC1, as found in human breast cancer cells, is of functional importance to repression of the p53 gene [5].
• The results suggest that expression of the PAM4-reactive antigen may represent an early event in the development of invasive pancreatic adenocarcinoma, and is unrelated to the VNTR peptide core epitopes of MUC1 [6].
• Studies in the immunobiology and pathology of IBD and colitis-associated colon cancer have been done in various mouse models but none could properly address the role of MUC1 due to low homology between the mouse and the human molecule [7].
• We propose that interactions of MUC1 and PDGFRbeta induce signal transduction events that influence the metastatic properties of pancreatic adenocarcinoma [8].

Psychiatry related information on MUC1

• Data from Bland-Altman differential plots suggest the presence of significant individual differences among individual samples, mainly in the region of high concentrations of MUC1 mucins [9].
• An appreciation of host defense mechanisms, particularly the antiadherence role of glycosaminoglycan (GAG) in the bladder mucin, reinforces clinical recognition of the bladder as the target organ for bacterial attack associated with urinary tract infection [10].
• 0. Long-term absence was significantly associated with DMS (OR = 2.1, 95%CI 1.0-4.6), EMA (OR = 5.6, 95%CI 1.0-28.7), sleeping poorly at night (OR= 2.6, 95%CI 1.4-5.0), and high depressive symptoms (OR = 2.0, 95%CI 1.0-3.7) according to the CES-D score of >16, after adjusting for multiple confounding variables [11].
• Is multi-impulsive bulimia a distinct type of bulimia nervosa: Psychopathology and EMA findings [12].
• The results of applying the PEM approach to synthesize the effect of self-control training on academic and social behavior showed that the treatment was highly or at least moderately effective [13].

High impact information on MUC1

• This region includes the gene GALNT3, which encodes a glycosyltransferase responsible for initiating mucin-type O-glycosylation [14].
• We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites [15].
• Overcoming MUC1 mucin-induced immunosuppression with IL-2 combined with active specific immunotherapy might be an effective immunotherapeutic strategy against human adenocarcinomas [16].
• This MUC1 mucin-induced suppression of T-cell responses can be reversed by the addition of exogenous IL-2 or anti-CD28 monoclonal antibody [16].
• A number of adenocarcinomas abundantly express and secrete underglycosylated MUC1 mucin [16].

Chemical compound and disease context of MUC1

• The DF3/MUC1 mucin-like glycoprotein is highly overexpressed in human carcinomas [17].
• Tyrosine kinase c-Src constitutes a bridge between cystic fibrosis transmembrane regulator channel failure and MUC1 overexpression in cystic fibrosis [18].
• Two factors potentially determining the consistent overexpression of sialyl-Le(x) antigen in colon carcinoma and metastases were investigated: (i) the expression of the mucins MUC1 and MUC2, known to carry sialyl-Le(x), by Northern blotting; (ii) the extent of sialic acid O-acetylation, by Western blotting and HPLC [19].
• Especially ductal and lobular carcinomas were strongly MUC1- and sialyl Lewisa-positive, whereas MUC2 binding was significantly elevated in mucinous neoplasms [20].
• Expression of the MUC1 gene and sialyl Lewis X was characteristic to all five cell lines derived from clear cell adenocarcinomas [21].

Biological context of MUC1

• Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells [22].
• Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components [23].
• GSK3beta-mediated phosphorylation of MUC1 had no apparent effect on beta-catenin levels or the transcriptional coactivation function of beta-catenin [17].
• The gene expression of MUCs (MUC1-MUC8) may change characteristically during malignant transformation of epithelial tissues [24].
• The proteins comprising this complex are, thus, generated by alternative splicing from one and the same gene, namely the MUC1 gene [25].

Anatomical context of MUC1

• CONCLUSIONS: Increased gallbladder epithelial MUC1 mucin enhances cholelithogenesis by promoting gallbladder cholesterol absorption and impairing gallbladder motility in mice [26].
• Normal pancreatic ducts show homogeneous expression of MUC1 and MUC5B and heterogenous expression of MUC3 [27].
• Antibodies to ICAM-1 and to MUC1 inhibited adhesion of human and transfected mouse MUC1-positive cell lines to human umbilical vein endothelial cell monolayers and immobilized recombinant human ICAM-1-immunoglobulin fusion protein [28].
• In contrast, the transformed nonmalignant ovarian epithelial cell lines expressed only MUC1 and 5AC [4].
• MUC1 core peptide, recognized by monoclonal antibodies 139H2 and DF3, was highly expressed on apical membranes of bronchus, breast, salivary gland, pancreas, prostate, and uterus, and was sparsely expressed in gastric surface cells, gallbladder, small intestine, and colonic epithelium [2].

Associations of MUC1 with chemical compounds

• We report that the MUC1 C-terminal subunit associates with estrogen receptor alpha (ERalpha) and that this interaction is stimulated by 17beta-estradiol (E2) [1].
• Evidence that gallbladder epithelial mucin enhances cholesterol cholelithogenesis in MUC1 transgenic mice [26].
• GSK3beta binds directly to an STDRSPYE site in MUC1 and phosphorylates the serine adjacent to proline [17].
• The MUC1/Y isoform is devoid of the mucin domain and is a cell membrane protein that undergoes transphosphorylation on both serine and tyrosine residues [25].
• Recombinant tumor-associated MUC1 glycoprotein impairs the differentiation and function of dendritic cells [29].

Physical interactions of MUC1

• The results demonstrate that the c-Src SH2 domain binds directly to pYEKV and inhibits the interaction between MUC1 and GSK3 beta [30].
• Recent studies have demonstrated that the cytoplasmic domain of MUC1 interacts with beta-catenin [17].
• The results further demonstrate that MUC1 interacts with ZAP-70 [31].
• It has been shown previously that the MUC1 cytoplasmic domain interacts with the SH2 domain containing GRB2 protein, which transduces signals to ras, a protein which in its activated form can lead to cell transformation [32].
• FGF1 also induced binding of MUC1 to the heat shock protein 90 (HSP90) chaperone by a mechanism dependent on phosphorylation of the YEKV motif [33].

Enzymatic interactions of MUC1

• Human cathepsin L and the corresponding mouse enzyme in low-density endosomes were identified in vitro to catalyze this site-specific MUC1 proteolysis [34].
• The UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 (GalNAc-T3) has the epithelial gland-specific expression and catalyzes mucin-type O-glycosylation [35].

Regulatory relationships of MUC1

• CC extensively expressed MUC1 apomucin and focally expressed MUC2 apomucin [36].
• MUC1 oncoprotein stabilizes and activates estrogen receptor alpha [1].
• These effects were enhanced by MB2, an antibody against E-cadherin and blocked by monoclonal antibodies (MAbs) 214D4 or M8 against episialin [37].
• Surprisingly, suppression of MUC1 also inhibited expression of EGFR at both the mRNA and protein levels whereas the reciprocal effect was not observed [38].
• The results show that IL-7 up-regulates MUC1 on CD4+, CD8+, CD25+, CD69+, naive CD45RA+, and memory CD45RO+ T cells [39].

Other interactions of MUC1

• These antibodies reacted with the MUC2-derived peptide but not with MUC1- or MUC3-derived peptides [40].
• The incomplete forms of intestinal metaplasia, type II (n = 25) and type III (n = 16), expressed MUC1 and MUC5AC in every case, both in goblet and in columnar cells [41].
• Data showed that gp230 was distinct from MUC1 or CD44 [42].
• A nuclear factor that binds purine-rich, single-stranded oligonucleotides derived from S1-sensitive elements upstream of the CFTR gene and the MUC1 gene [43].
• All hyperplastic polyps displayed immunoreactivity for TFF1, MUC5AC, and MUC1 in more than 75 per cent of the cells [44].
• MUC1-mediated activation of IKKbeta is dependent on TAK1 and TAB2 [45].
• Collectively, these data indicate that PIASy may be a useful target for down-regulation of MUC1 expression in various contexts [46].

Analytical, diagnostic and therapeutic context of MUC1

• The expression of MUC1/ZD at the protein level in human tissues is demonstrated by Western blotting, immunohistochemistry, immunoprecipitation, and an ELISA [47].
• The availability of large quantities of this MUC1 glycoform will allow the evaluation of its efficacy as an immunogen for immunotherapy of MUC1/STn-expressing tumors [48].
• Molecular cloning and analysis of the mouse homologue of the tumor-associated mucin, MUC1, reveals conservation of potential O-glycosylation sites, transmembrane, and cytoplasmic domains and a loss of minisatellite-like polymorphism [49].
• However, adoptive transfer of these CTLs was able to completely eradicate MUC1-expressing injectable tumors in MUC1 transgenic mice, and these mice developed long-term immunity [50].
• Correlative studies also indicate the presence of soluble forms of MUC1 in cell culture supernatants in vitro and in bodily fluids in vivo [51].

References