Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:O95477 (membrane-bound)
29,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormalities of mucin-type glycoproteins have been described in lung cancers, but their molecular basis is unknown. In this study, mucin-core-peptide-specific antibodies and cDNA probes were used to determine the relative expression of mucin genes corresponding to one membrane-bound mucin (MUC1), two intestinal mucins (MUC2 and MUC3), and one tracheobronchial mucin (MUC4) in normal (nonneoplastic) lung, and in lung neoplasms. Normal lung tissues exhibited a distinct pattern of mucin gene expression, with high levels of MUC1 and MUC4 mRNA and low to absent levels of MUC2 and MUC3 mucin immunoreactivity and mRNA. In contrast, lung adenocarcinomas, especially well-differentiated cancers, exhibited increased MUC1, MUC3, and MUC4 mRNA levels. Lung squamous-cell, adenosquamous, and large-cell carcinomas were characterized by increased levels of MUC4 mucin only. We conclude that the expression of one membrane-bound and several secretory-type mucins is independently regulated and markedly altered in lung neoplasms. The frequent occurrence of increased MUC4 transcripts in a variety of non-small-cell lung cancers indicates the potential importance of this type of mucin in lung cancer biology.
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PMID:Membrane-bound (MUC1) and secretory (MUC2, MUC3, and MUC4) mucin gene expression in human lung cancer. 863 91

The MUC genes encode epithelial mucins. Eight different human genes have been well characterized, and two others identified more recently. Among them, a family of four genes, expressed in the respiratory and digestive tracts, is clustered to chromosome 11p15.5; and these genes encode gel-forming mucins which are structurally related to the superfamily of cystine-knot growth factors. A second group is composed of three independent genes encoding various isoforms of mucins including membrane-bound mucins associated to carcinomas. In this second group, MUC3 and MUC4 encode large apomucins containing EGF-like domains.
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PMID:[MUC genes: a superfamily of genes? Towards a functional classification of human apomucins]. 1085 60

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.
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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.
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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.
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PMID:Potentiation of metastasis by cell surface sialomucin complex (rat MUC4), a multifunctional anti-adhesive glycoprotein. 1091 86

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.
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PMID:Alternate splicing at the 3'-end of the human pancreatic tumor-associated mucin MUC4 cDNA. 1113 23

Hypersecretion of mucin is a common feature of chronic and mucoid otitis media which may play an important role in hearing loss. The mechanisms controlling mucin secretion in the middle ear are not completely understood. Our reverse transcriptase-polymerase chain reaction results demonstrate that mRNAs of MUC1, MUC2, MUC3, MUC4 and MUC5AC are expressed in normal rat middle ear mucosa. Moreover, the expression of mRNA of the secretory mucins MUC2, MUC3 and MUC5AC was threefold lower in normal middle ear mucosa than that in the intestine or trachea. In contrast, expression of the membrane-bound mucins MUC1 and MUC4 was approximately the same in both middle ear mucosa and the intestine or trachea. MUC5AC proteins were also identified immunohistochemically in normal rat middle car epithelium. The methodology used in this study provides useful baseline information for investigation of the mechanisms of regulation of mucin gene expression during otitis media.
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PMID:Detection of mucin gene expression in normal rat middle ear mucosa by reverse transcriptase-polymerase chain reaction. 1127 Apr 93

Lung adenocarcinomas are heterogeneous clinically and histologically. Expression of the mucin genes was analyzed as a molecular marker of glandular cytodifferentiation in primary lung adenocarcinomas. Expression was correlated with histopathologic subtypes of World Health Organization classification with the aim of investigating the histogenesis of primary lung adenocarcinomas. Thirty-four primary lung adenocarcinomas were examined by in situ hybridization for mucin gene expression (MUC1-4, MUC5AC, MUC5B, MUC6-7) and by immunohistochemistry for MUC5AC and MUC5B apomucin expression. Mucinous bronchioloalveolar carcinoma (BAC) had a homogeneous pattern of mucin gene expression different from those of other types of lung adenocarcinoma, involving secreted mucins (MUC5AC, MUC5B, and MUC6) and membrane-bound mucins (MUC1, MUC3, and MUC4). Non-BAC adenocarcinoma and mucinous BAC aberrantly expressed mucin genes MUC3, and MUC3 and MUC6, respectively, which are undetectable in normal fetal and adult lung. Our results show the particular phenotype of mucin gene expression in mucinous type of BACs and the heterogeneous expression of respiratory and nonrespiratory mucins in the other types. This finding supports the theory of a common progenitor cell with the potential of multicellular differentiation. From a practical point of view, the aberrant expression of MUC3 and MUC6 could serve as a diagnostic marker in the management of the mucinous type of bronchioloalveolar carcinomas. HUM PATHOL 32:274-281.
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PMID:Mucinous bronchioloalveolar carcinomas display a specific pattern of mucin gene expression among primary lung adenocarcinomas. 1127 35

Mucins are glycoproteins synthesized by epithelial cells and thought to promote tumor-cell invasion. Eight human mucin genes have been well characterized: MUC2, MUC5AC, MUC5B, MUC6 map to 11p15.5 and encode secretory gel forming mucins while MUC1, MUC3, MUC4, MUC7 are scattered on different chromosomes and encode membrane-bound or secreted mucins. The expression pattern of the mucin genes is complex in normal airways involving six genes, mainly MUC5AC and MUC5B in mucus-producing cells and MUC4 in a wide array of epithelial cells. MUC5AC overexpression in metaplasia, dysplasia and normal epithelium adjacent to squamous cell carcinoma provides additional arguments for a mucous cell origin of preneoplastic squamous lesions. MUC5AC and MUC5B expression is related to mucus formation in adenocarcinomas. Mucinous bronchioloalveolar carcinoma (BAC) has a particular pattern of mucin gene expression indicating that it has sustained a well-differentiated phenotype similar to the goblet cell, correlated with distinctive features i.e. a noninvasive pattern and a better prognosis than nonBACs. MUC4 is the earlier mucin gene expressed in the foregut, before epithelial differentiation and is expressed independently of mucus secretion both in normal adult airways and carcinomas. These findings are in favor the histogenetic theory of non-small-cell carcinoma originating from a pluripotent mucous cell.
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PMID:Normal respiratory mucosa, precursor lesions and lung carcinomas: differential expression of human mucin genes. 1157 57

The cells of living organisms in contact with the external environment are constantly attacked by different kinds of substances such as micro-organisms, toxins, and pollutants. With evolution, defense mechanisms, such as the secretion of mucus has been developed. Mucins are the main components of mucus. They are synthesized and secreted by specialized cells of the epithelium and in some case, by non mucin-secreting cells. Little was known about the structure of mucins until a decade ago. This is principally due to heavy glycosylation of mucins, which complicated their analysis. With the application of molecular biological methods, structures of the mucin core peptides (apomucins) are beginning to be elucidated. A total of eleven human mucin (MUC) genes have been identified and numbered in chronological order of their description: MUC1-4, MUC5AC, MUC5B, MUC6-8, and MUC11-12. Of these, the complete cDNA sequence are published only for six mucins MUC1, MUC2, MUC4, MUC5B, MUC5AC, and MUC7. Human mucin genes, in general, show three common features: I) a nucleotide tandem repeat domain; II) a predicted peptide domain containing a high percentage of serines and threonines; III) complex RNA expression. The tandem repeats in mucins make up the majority of the backbone. Related to their structure, mucins can be classified in three distinct sub-families: gel-forming, soluble, and membrane-bound. Each member from one family possesses common characteristics and probably specific functions. For a long time, they were thought to have the unique function of protecting and lubricating the epithelial surfaces. The study of the mucins structure as well as the relationship between structure and function show that mucins also possess other important functions, such as growth, direct implication in the fetal development, the epithelial renewal and differentiation, the epithelial integrity, carcinogenesis, and metastasis. This review presents the actual knowledge on the mucins structure and the best-characterized function related to their structure.
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PMID:Structural organization and classification of the human mucin genes. 1157 69


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