Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O95477 (membrane-bound)
 29,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The membrane-bound MUC1 mucin is expressed in normal mucosas and the aberrant expression of its under-glycosylated forms has been reported in carcinomas from different sites. Several studies have provided conflicting evidence regarding the relationship between MUC1 expression and outcome in cancer patients. In this study, we investigated the immunohistochemical expression of MUC1 epitopes, using 2 monoclonal antibodies (MAbs): HMFG1, which reacts with the fully glycosylated MUC1, was studied in 73 gastric carcinomas; and SM3, which recognises an under-glycosylated form of MUC1, was studied in 180 cases. HMFG1 stained the antrum foveolar cells and the body glands of normal gastric mucosa, whereas SM3 reactivity was restricted to the perinuclear region of some foveolar cells. Type I intestinal metaplasia exhibited down-regulation of MUC1 expression using both MAbs. Every gastric carcinoma was stained with HMFG1 and 80% with SM3. High levels of expression of HMFG1 were associated with lymphatic invasion, nodal metastatization, and advanced pTNM staging. The expression of SM3 was associated with the histologic (solid) type of carcinoma, expanding growth pattern, wall penetration, lymphatic invasion and age of the patients. Despite a trend for a poor outcome in patients with tumours (over)expressing MUC1 mucin, the survival of the patients evaluated by univariate and multivariate analysis was not significantly associated with the levels of expression of HMFG1 or with the expression of the SM3 epitope. We conclude that (a) MUC1 expression, namely of the SM3 cancer-associated epitope, is significantly associated with several aspects of gastric cancer development and progression; and (b) MUC1 expression should not be used as a prognostic marker in patients with gastric carcinoma.
 ...
PMID:Expression of fully and under-glycosylated forms of MUC1 mucin in gastric carcinoma. 969 34

The ocular surface, which is among the most accessible and vulnerable tissues in mammals, is protected by a complex tear film composed of lipid, aqueous and mucin layers. In spite of its importance, the molecular nature of the mucin contribution remains uncertain. Since membrane mucins have been implicated in the protection of other epithelia, we have analysed rat corneal and conjunctival tissues for sialomucin complex (SMC), a membrane mucin found at the apical epithelial cell surfaces in the airway and uterus. Using Northern and Western blot analyses, SMC expression was found in both ocular tissues, being particularly abundant in the cornea. In contrast with the other known membrane mucin, MUC1, SMC was localized more heavily towards the apical surface of the epithelial cells. SMC in ocular surface epithelia was produced in both soluble and membrane forms, the latter being found predominantly in the most superficial cells and at apical surfaces. The soluble form was found loosely adsorbed to apical cell surfaces, particularly of the cornea, as indicated by a mild rinsing protocol. Finally, the tear fluid contained substantial amounts of SMC. From these results, we propose a new model for tear mucin components in which SMC is expressed at the apical ocular surface in both membrane-bound and adsorbed soluble forms to provide a direct protective barrier. SMC secreted into the tear fluid may also participate in maintaining the stability of the preocular tear film by acting with other secreted mucins to determine the physical properties and protective behaviour of the tear film.
 ...
PMID:Sialomucin complex at the rat ocular surface: a new model for ocular surface protection. 976 47

Abnormalities in mucin-type glycoprotein expression have been documented in a variety of cancers, identifying these molecules as targets for immunologically based therapies and prognostic/diagnostic assays. We examined the expression of the membrane-bound MUC1 mucin in normal, histologically atypical, and neoplastic lung to determine its potential contribution to lung carcinogenesis. In vivo, intense MUC1 immunoreactivity was present in normal type II pneumocytes as well as in a range of atypical lesions derived from type II cells and >60% of primary and metastatic non-small cell lung cancers. Expression was not associated with altered survival, although it was highly correlated with the adenocarcinoma histology. A carcinogenesis model using 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone-exposed hamsters revealed that MUC1 mRNA increased prior to the histological appearance of tumors. In vitro studies using MUC1 expressing non-small cell lung cancer cell lines revealed that differentiation away from a type II cell lineage was associated with dramatic down-regulation of MUC1. We propose that MUC1 is a powerful new marker for the type II pneumocyte cell lineage that allows us to follow the type II pneumocyte lineage during the process of lung carcinogenesis.
 ...
PMID:MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis. 985 98

Intrahepatic calculi is characterized by an intractable course and frequent recurrences, requiring multiple operative interventions. Chronic proliferative cholangitis, an active and long-standing inflammation of the stone-containing bile ducts with the hyperplasia of epithelia and the proliferation of the duct-associated mucus glands, may underlie the complex nature of the disease. In terms of the pathophysiology, interest has been focused on the role of secretory low-molecular-weight phospholipases A2 (sPLA2s) as inflammatory mediators or factors modulating cell functions via their specific sPLA2-receptor, and also on the production and secretion of altered mucin molecules from the inflamed bile ducts. In search of factors involving chronic proliferative cholangitis, the sPLA2 isoforms in the bile such as the pancreatic-type sPLA2 (group IB sPLA2) and the arthritic-type sPLA2 (group IIA sPLA2), were assayed to correlate protein masses of the sPLA2s with alterations in biliary composition. Furthermore, the steady-state messenger RNA (mRNA) levels of the sPLA2s, the membrane-bound sPLA2-receptor, cystic fibrosis transmembrane conductance regulator (CFTR), and mucin core polypeptide (MUC) genes in the bile ducts were assayed by reverse- transcriptase polymerase chain reaction (RT-PCR). Immunoreactive sPLA2-IB and sPLA2-IIA levels were significantly higher in the bile from the stone-containing hepatic ducts (2315 +/- 677 for sPLA2-IB; 281 +/- 42 for sPLA2-IIA ng/dL, mean +/- SEM; n = 20) than in the ductal bile from gallbladder stone patients (609 +/- 92, P <.01; 22 +/- 2, P <.01; n = 24). The increased sPLA2 levels were associated with a concomitant increase in lysophosphatidylcholine, prostaglandin E2 (PGE2), and total mucin concentrations. The affected bile ducts showed an increased mRNA level of sPLA2-IB and sPLA2-IIA compared with the ducts from control subjects, in whom the mRNAs of the sPLA2-receptor and other sPLA2 isoforms, such as groups V and X sPLA2s, were coincidently expressed. Reflecting the increased amounts of total biliary mucins, the affected ducts showed an increase in mRNA levels of CFTR as well as MUC2, MUC3, MUC5AC, MUC5B, and MUC6 compared with the ducts from control subjects. In intrahepatic calculi, an enhanced expression of the sPLA2s and their possible cross-talk via sPLA2-receptor may be of pathophysiological significance for the chronic proliferative cholangitis, in association with the enhanced CFTR expression and the alterations in mucin gene expression in the bile ducts, probably through potentiating arachidonate metabolism with associated biliary alterations favoring growth of preexisting stones and even further progressions.
 ...
PMID:Secretory low-molecular-weight phospholipases A2 and their specific receptor in bile ducts of patients with intrahepatic calculi: factors of chronic proliferative cholangitis. 1009 42

The MUC3 gene encodes a large, glycosylated mucin produced by intestinal epithelial cells to form a protective barrier against the external environment. Recently published cDNA sequences for the carboxyl-terminal region of MUC3 polypeptide indicated that rodent Muc3 possesses two epidermal growth factor (EGF)-like domains, and putative transmembrane and cytoplasmic domains, whereas the sequence of human MUC3 predicted termination after the first EGF-like domain. Here we describe the complete genomic sequence encompassing the carboxyl terminal region of human MUC3, revealing the boundaries of 11 exons. RT-PCR and cDNA library cloning experiments indicate that the gene is alternatively spliced, yielding a major membrane-bound form as well as multiple soluble forms. Thus, this work indicates that both membrane-bound and soluble MUC3 mucin proteins are produced by alternative splicing of a single gene. A potentially important polymorphism involving a Tyr residue with a proposed role in signalling is described as well.
 ...
PMID:Genomic organization and structure of the 3' region of human MUC3: alternative splicing predicts membrane-bound and soluble forms of the mucin. 1051 48

Human mucin genes include membrane-bound mucins (MUC1, MUC3, MUC4) and secretory mucins (MUC2, MUC5AC, MUC5B, MUC6). Our aim was to determine mucin gene expression in human gallbladder cell lines, normal gallbladder from liver donors (N = 7) and surgical specimens with mild chronic cholecystitis (N = 29), chronic cholecystitis (N = 48), and acute and chronic cholecystitis (N = 27). MUC1 mRNA was ubiquitous; however, only rare MUC1 immunoreactivity was detected. MUC3, MUC5AC, MUC5B, and MUC6 mRNA were present in all gallbladder specimens and cell lines examined. Prominent MUC3, MUC5AC, MUC5B, and MUC6 immunoreactivity was present in 86-100% of normal gallbladders. The frequency of MUC5AC reactivity was decreased in specimens with acute cholecystitis (P < 0.05). In contrast, MUC2-reactivity was absent in normal gallbladder and present in 53.8% of acute cholecystitis specimens (P < 0.05). Surface epithelium is characterized by MUC3, MUC5AC, and MUC5B, whereas deeper mucosal folds display MUC5B and MUC6 immunoreactivity. Gallbladder epithelium demonstrates a unique and diverse pattern of mucin core proteins that becomes altered with increasing degrees of inflammation.
 ...
PMID:Altered mucin core peptide expression in acute and chronic cholecystitis. 1087 17

The MUC4 mucin gene encodes a putative membrane-anchored mucin with predicted size of 930 kDa, for its 26.5-kb allele. It is composed of two regions, the 850-kDa mucin-type subunit MUC4alpha and the 80-kDa membrane-associated subunit MUC4beta. In this study, we cloned and characterized unique MUC4 cDNA sequences that differ from the originally published sequence. Eight alternative splice events located downstream of the central large tandem repeat array generated eight new, distinct cDNAs. The deduced sequences of these MUC4 cDNAs (sv1-MUC4 to sv8-MUC4, the full length cDNA being called sv0-MUC4) provided seven distinct variants, five secreted forms and two membrane-associated forms. Furthermore, two other alternative splicing events located on both sides of the tandem repeat array created two variants, MUC4/Y and MUC4/X, both lacking the central tandem repeat. Therefore, MUC4 can be expressed in three distinct forms, one membrane-bound, one secreted, and one lacking the hallmark feature of mucin, the tandem repeat array. Although no specific function has yet been discovered for the family of proteins putatively produced from the unique MUC4 gene, we suspect that the MUC4 proteins may be implicated in the integrity and renewal of the epithelium.
 ...
PMID:Alternative splicing generates a family of putative secreted and membrane-associated MUC4 mucins. 1088 Sep 78

Sialomucin complex (SMC), a rat homologue of the human mucin MUC4, is a large membrane-bound mucin complex, originally isolated from highly metastatic ascites 13762 mammary adenocarcinoma cells. When overexpressed, SMC exerts potent anti-adhesive effects, which sterically disrupt molecular interactions for cell-cell and cell-ECM adhesions. SMC similarly suppresses anti-tumor immunity by inhibition of interactions between cytotoxic lymphocytes and target tumor cells. Previously, recombinant cDNAs for SMC were transfected and inducibly expressed in A375 human melanoma cells using a tetracycline-responsive expression system. In the current studies, we investigated the role of MUC4/SMC in tumor metastasis by regulating SMC expression of tumor transplants in vivo. Intravenous injection of SMC-overexpressing cells resulted in substantially greater lung metastasis than injection of SMC-repressed cells. Injection of SMC-overexpressing cells followed by in vivo downregulation of SMC did not lower the frequency of lung metastasis. Growth of the micrometastatic lesions was the same for all 3 cases in short-term (3-week) assays. Further, subcutaneous injection of A375 cells followed by in vivo induction of SMC overexpression within the solid tumor resulted in spontaneous distant metastasis. These studies suggest that SMC potentiates metastasis by contributing to the establishment of metastatic foci. These studies directly demonstrate for the first time that tumor metastasis can be modulated by the regulation of MUC4/SMC expression.
 ...
PMID:Potentiation of metastasis by cell surface sialomucin complex (rat MUC4), a multifunctional anti-adhesive glycoprotein. 1091 86

Parasite-derived mucin-like molecules might be involved in parasite attachment to and invasion of host cells. In addition, parasites might secrete mucin-degrading enzymes, enabling the penetration of protective mucus gels that overlie the mucosal surfaces of their potential hosts. Furthermore, they might generate binding ligands on the membrane-bound mucins of host cells by using specific glycosidases. It is possible that host mucins and mucin-like molecules prevent the establishment of parasites or facilitate parasite expulsion. They might also serve as a source of metabolic energy and adhesion ligands for those parasites adapted to exploit them. Sally Hicks and colleagues here review the biochemical properties of mucins and mucin-like molecules in relation to interactions (established and putative) between protozoan parasites and their hosts.
 ...
PMID:The role of mucins in host-parasite interactions. Part I-protozoan parasites. 1106 58

MUC4 is a membrane-bound mucin and is considered as the human homologue of the rat sialomucin complex (SMC). The deduced structural organization of the wild type-MUC4 cDNA (WT-MUC4) sequence revealed two subunits: a large amino mucin type subunit (MUC4alpha) and a transmembrane subunit (MUC4beta). MUC4beta is a membrane-bound growth factor like subunit and contains three EGF-like domains. The MUC4 gene is expressed in several normal tissues like trachea, lung, and testis. It is not expressed in a normal human pancreas; however, its dysregulation results in high levels of expression in pancreatic tumors and tumor cell lines. Recently, we have demonstrated the presence of alternative splice events in the 3'-end of the MUC4 cDNA that generated new putative variants (sv1-sv10) in normal human testis and in a pancreatic tumor cell line (HPAF). In search of MUC4 variant(s) that are specific to pancreatic adenocarcinoma, we investigated the splicing phenomena in the MUC4 cDNA sequence by using a large panel of pancreatic tumor cell lines. We have identified ten alternative splice events located downstream to the central large tandem repeat domain. These splice events generated 12 variant species (sv4, sv9, sv10-18, and sv21) of MUC4 cDNAs. The deduced amino acid sequence of these variant MUC4 cDNAs revealed two distinct types: a family of secreted and a membrane-associated variant form. Among the members of MUC4 secreted variant family, three (sv4, sv12, and sv13) of ten showed a short 144 residue COOH-terminus compared to 1154 residues in WT-MUC4. The variants with this short COOH-terminus (144 residues) was found in 37% (4/11) of the tumor lines. The putative membrane-bound variant sv10 was detected in 37% (4/11) pancreatic tumor cell lines but not in any normal human tissues. In conclusion, we have identified novel splice variant(s) of MUC4 in pancreatic adenocarcinoma.
 ...
PMID:Alternate splicing at the 3'-end of the human pancreatic tumor-associated mucin MUC4 cDNA. 1113 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>