Human Mucin Genes MUC2, MUC3,MUC4, MUC5AC, MUC5B, andMUC6 Express Stable and Extremely Large mRNAs and Exhibit a Variable Length Polymorphism

Debailleul, Virginie; Laine, Anne; Huet, Guillemette; Mathon, Pascal; D'Hooghe, M; Aubert, Jean; Porchet, Nicole

doi:10.1074/jbc.273.2.881

Cited by 104 publications

(82 citation statements)

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“…4), which is in line with the known polymorphism that is characteristic of the mucin genes as demonstrated for MCF-7 cells by others. 31,37 Treatment with ET-18-OMe did not significantly alter the episialin mRNA levels.…”

Section: Effect Of Et-18-ome On the Expression Of Episialin And E-cadmentioning

confidence: 90%

“…31 Briefly, RNA samples were denaturated and then fractionated by electrophoresis through a 0.9% agarose denaturating gel, followed by transfer onto Hybond TM -N ϩ membrane. The episialin and GAPDH probe 32 were labeled with [ 32 P] dCTP using a commercial random-primed labeling kit (Boehringer Mannheim, Mannheim, Germany) in accordance with the manufacturer's protocol.…”

Section: Northern Blot Analysis Of Episialinmentioning

confidence: 99%

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Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

et al. 2001

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1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18 Key words: alkyl-lysophospholipid; E-cadherin; episialin; adhesion; invasion1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OMe) interacts with cell membranes, thereby modulating phospholipid metabolism, interfering with signal transduction, inducing apoptosis and differentiation and regulating invasion. 1 On solid substrate, the E-cadherin/catenin complex is implicated in the cell-cell adhesion of 2 variants of the MCF-7 human breast cancer cell line family, coined MCF-7/AZ and MCF-7/6. In suspension, however, MCF-7/6 cells are adhesion-deficient while MCF-7/AZ cells are adhesion-proficient. Treatment with ET-18-OMe caused antithetic effects on the 2 types of MCF-7 cells. ET-18-OMe restored the E-cadherin function in the adhesiondeficient MCF-7/6 cells, whereas it caused a decrease in cellular aggregation of the adhesion-proficient MCF-7/AZ cells. The latter effects could not be explained by changes in sialylation of Ecadherin. 2 Antithetic effects on invasion have also been reported: ET-18-OMe inhibited invasion of constitutively invasive cells, [3][4][5][6] whereas it induced invasion of otherwise noninvasive cells. 7,8 Inhibition of invasion in the presence of ET-18-OMe was explained by induction of host tissue resistance, 9 but the antithetic effects on cell-cell adhesion and the invasion-promoting effect of ET-18-OMe have not been explained.Adhesion and invasion are the result of a balance between promoter and suppressor molecules modulated by multiple intraand extracellular factors. The presence of the anti-adhesion molecule episialin on the 2 types of MCF-7 cells was observed in a previous study. 2 The aim of our study was to see whether ET-18-OMe affects invasion and adhesion through modulation of episialin and E-cadherin.Episialin is a heterodimeric molecule composed of a membrane anchor and an extracellular moiety. The membrane anchor consists of a cytoplasmatic domain of 68 amino acids and a transmembrane domain. The extracellular moiety consists of a large mucin domain containing a large number of O-linked glycans. 10 The carbohydrate side chains carry many sialic acid residues conveying a highly negative charge upon episialin. 11 Episialin is located at the apical surface of most glandular epithelial cells; it is over-expressed in carcinomas, often distributed over the entire cell surface. 11 Overexpression of episialin inhibits integrin-mediated cell adhesion to

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Section: Effect Of Et-18-ome On the Expression Of Episialin And E-cadmentioning

confidence: 90%

Section: Northern Blot Analysis Of Episialinmentioning

confidence: 99%

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

et al. 2001

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“…Tissue samples were manually ground to a fine powder in liquid nitrogen with mortar and pestle and resuspended in modified guanidinium isothiocyanate (GITC) buffer (Debailleul et al, 1998). Cultured adenocarcinoma cells at subconfluence were rinsed twice in ice-cold phosphate-buffered saline and solubilized in GITC buffer.…”

Section: Rna Isolationmentioning

confidence: 99%

“…Cultured adenocarcinoma cells at subconfluence were rinsed twice in ice-cold phosphate-buffered saline and solubilized in GITC buffer. Total RNA was extracted from pancreatic tumour cell lines, immortalized normal pancreatic ductal cells and normal pancreatic tissue samples by using guanidine isothiocyanate-cesium chloride ultracentrifugation method, as described previously (Debailleul et al, 1998). RNA concentration was measured spectrophotometrically and its integrity was analysed by electrophoresis on a formaldehyde agarose gel.…”

Section: Rna Isolationmentioning

confidence: 99%

MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms

et al. 2006

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MUC4 mucin is a high molecular weight transmembrane glycoprotein that plays important roles in tumour biology. It is aberrantly expressed in pancreatic adenocarcinoma, while not being detectable in the normal pancreas. Previous studies have demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that is defective in CF, is implicated in multiple cellular functions, including gene regulation. In the present study, using a CFTR-defective pancreatic cancer cell line and its derived subline expressing functional CFTR, we report that MUC4 expression is negatively regulated by CFTR. Short-interfering RNA (siRNA)-mediated silencing of CFTR also leads to an increased expression of MUC4. Additionally, our results suggest that CFTR-mediated regulation of MUC4 is cell densitydependent and is achieved by transcriptional and posttranslational mechanisms. Moreover, in a panel of pancreatic cancer cell lines and normal pancreas, we observed that CFTR was downregulated in pancreatic cancer cells and negatively correlated with MUC4 in most cases. An aberrant expression of MUC4 was also detected in the CF pancreas. Downregulation of CFTR in pancreatic adenocarcinoma and its inverse association with the tumour-linked mucin, MUC4, indicate novel function(s) of CFTR in pancreatic tumour biology and suggest the implication of new signalling pathway(s) in MUC4 regulation.

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“…32 RNA was reverse transcribed using 1 st -Strand™cDNA Synthesis Kit (ClonTech, Palo Alto, CA) and RT-PCR analysis was performed for the amplification of E-cadherin, MUC1 and MUC5AC.…”

Section: Rt-pcrmentioning

confidence: 99%

Requirement of both mucins and proteoglycans in cell‐cell dissociation and invasiveness of colon carcinoma HT‐29 cells

Truant

Bruyneel

Gouyer

et al. 2003

Intl Journal of Cancer

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Key words: colon carcinoma cells; E-cadherin; mucins; heparan sulfate proteoglycansEpithelial E-cadherin, a component of the adherens junctions, is crucial for the organization and maintenance of differentiated epithelia. 1 The extracellular NH2-terminal domain of this transmembrane glycoprotein mediates cell-cell adhesion in a homophilic and Ca 2ϩ -dependent way. The COOH-terminal domain binds to the actin cytoskeleton via ␣-catenin and ␤-catenin or plakoglobin. 2 Studies in cancer cell lines have shown that changes in the structure or in the expression of the components of the E-cadherin/␤-catenin complex result in the suppression of cell-cell adhesion and in the expression of an invasive phenotype. [3][4][5][6][7][8] In cancer, the maintenance of the epithelia is lost and dissociation of cells is associated with metastatic dissemination. This phenomenon can occur through a decrease in the expression level of E-cadherin and, regarding colon cancer, such decrease has been related to the tumor grade and clinical outcome. 9 At the genomic level, loss of E-cadherin expression does not occur as a result of mutation of E-cadherin gene, whereas mutations of ␤-catenin were found in a small proportion of colon cancers. 10 -12 In another way, E-cadherin-mediated cell-cell adhesion may be modulated by the mucin-like glycoprotein MUC1, which is often overexpressed in cancer. MUC1, also termed episialin, is a membrane-associated glycoprotein composed of a membrane anchor and a mucin-like ectodomain. 13 In human ZR-75-1 breast cancer cells, the cytoplasmic domain of MUC1 was shown to bind ␤-catenin, leading to a decrease of E-cadherin-catenin complex and an anti-adhesion effect. 14 On the other hand, MUC1 was shown to cause steric hindrance of adhesion molecules like E-cadherin, through its large negatively charged extracellular domain, which contains many oligosaccharide side chains. 15,16 Proteoglycans were also shown to disturb the function of E-cadherin through steric hindrance in variants of the murine mammary gland cell line NMuMG and the canine epithelial kidney cell line MDCK. 17 During colorectal carcinogenesis, the expression of MUC1 was found upregulated, particularly in later stages of the disease. 18 -20 On the other hand, de novo appearance of a secreted mucin normally found in the stomach, MUC5AC, has been described in colon carcinomas. [21][22][23] Thus, mucinous differentiated cells are present in colorectal carcinomas and more particularly in mucinous carcinomas and in signet ring cell carcinomas. Until now, the significance of a differentiation characteristic into a mucin-secreting phenotype with regard to the tumor development is still unknown.To investigate the role of mucins in the invasive properties of colon carcinoma cells, the HT-29 cell line is an appropriate model, as the cells of this cell line express different phenotypes: besides a majority of undifferentiated cells (Ͼ95%), a small proportion of cells presents a capacity to differentiate into a mucinous phenotype or into an enterocyte-like ...

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Human Mucin Genes MUC2, MUC3,MUC4, MUC5AC, MUC5B, andMUC6 Express Stable and Extremely Large mRNAs and Exhibit a Variable Length Polymorphism

Cited by 104 publications

References 64 publications

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms

Requirement of both mucins and proteoglycans in cell‐cell dissociation and invasiveness of colon carcinoma HT‐29 cells

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