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Nicole Porchet - One of the best experts on this subject based on the ideXlab platform.
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structural organization and classification of the human mucin genes
Frontiers in Bioscience, 2001Co-Authors: Nicolas Moniaux, Nicole Porchet, Fabienne Escande, J P Aubert, Surinder K. BatraAbstract: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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normal respiratory mucosa precursor lesions and lung carcinomas differential expression of human mucin genes
Frontiers in Bioscience, 2001Co-Authors: Mariechristine Copin, Fabienne Escande, J P Aubert, Marie-pierre Buisine, L Devisme, Xavier Leroy, B Gosselin, Nicole PorchetAbstract: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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developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands i stomach a relationship to gastric carcinoma
Journal of Histochemistry and Cytochemistry, 2000Co-Authors: Marie-pierre Buisine, Nicole Porchet, Jean-pierre Aubert, Mariechristine Copin, L Devisme, V Maunoury, Elisabeth Deschodt, Bernard GosselinAbstract:Studies were undertaken to provide information regarding cell-specific expression of mucin genes in stomach and their relation to developmental and neoplastic patterns of epithelial cytodifferentiation. In situ hybridization was used to study mRNA expression of eight mucin genes (MUC1-4, MUC5AC, MUC5B, MUC6, MUC7) in stomach of 13 human embryos and fetuses (8-27 weeks' gestation), comparing these with normal, metaplastic, and neoplastic adult tissues. These investigations have demonstrated that MUC1, MUC4, MUC5AC, MUC5B, and MUC6 are already expressed in the embryonic stomach at 8 weeks of gestation. MUC3 mRNA expression can be observed from 10.5 weeks of gestation. MUC2 is expressed at later stages, concomitant with mucous gland cytodifferentiation. Normal adult stomach is characterized by strong expression of MUC1, MUC5AC, and MUC6, less prominent MUC2, and sporadic MUC3 and MUC4, without MUC5B and MUC7. Intestinal metaplasia is characterized by an intestinal-type pattern with MUC2 and MUC3 mRNA expression. Gastric carcinomas exhibit altered mucin gene expression patterns with disappearance of MUC5AC and MUC6 mRNAs in some tumor glands, abnormal expression of MUC2, and reappearance of MUC5B mRNAs. In conclusion, we have observed that patterns of mucin gene expression in embryonic and fetal stomach could show similarities with some gastric carcinomas in adults. Differences in mucin gene expression in developmental, metaplastic, and neoplastic stomach compared to normal adult stomach suggest a possible regulatory role for their products in gastric epithelial cell proliferation and differentiation.
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transdermal nicotine decreases mucosal il 8 expression but has no effect on mucin gene expression in ulcerative colitis
Inflammatory Bowel Diseases, 1998Co-Authors: Beatrice Louvet, Nicole Porchet, Marie-pierre Buisine, Jean-pierre Aubert, Pierre Desreumaux, William J Tremaine, Monique Capron, Antoine Cortot, Jeanfrederic Colombel, William J SandbornAbstract:Abstract Our goal was to determine the effect of transdermal nicotine on cytokine and mucin gene transcription in ulcerative colitis (UC). Sixty-four nonsmoking patients with active UC were randomly assigned to transdermal nicotine (maximum dose 22 mg/day) or placebo for 4 weeks. Clinical assessment and colonic mucosal biopsies were obtained at entry and after 4 weeks. Inflammatory and immunoregulatory cytokines were assessed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR). Based on this initial screen. IL-8 mRNA levels were measured by RT-competitive PCR. MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 mRNA concentrations were measured by quantitative dot blot analysis. Cytokine mRNA expression, except for IL-8, was similar in all patients. IL-8 mRNA levels were significantly decreased in the colonic mucosa of nicotine-treated patients who improved (p = 0.04). IL-8 mRNA values were similar before and after treatment in nonresponding nicotine-treated patients and in all placebo-treated patients. Mucin gene expression was similar in all patient groups. Beneficial effects of transdermal nicotine in active UC may result from decrease of IL-8 expression at the transcriptional level. Transdermal nicotine has no effect on mucin gene transcription.
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human mucin genes muc2 muc3 muc4 muc5ac muc5b and muc6 express stable and extremely large mrnas and exhibit a variable length polymorphism an improved method to analyze large mrnas
Journal of Biological Chemistry, 1998Co-Authors: Virginie Debailleul, Jean-pierre Aubert, Anne Laine, Guillemette Huet, Pascal Mathon, Maud Collyn Dhooghe, Nicole PorchetAbstract:Abstract Of the nine mucin genes that have been characterized, only MUC1 and MUC7 have been fully sequenced, and their transcripts can be detected as distinct bands of predicted size by Northern blot analysis. In contrast, the RNA patterns observed for each of the other MUC genes have usually shown a very high degree of polydispersity. This polydispersity has been believed to be one of the typical features of the mucin mRNAs, but until now, its origin has remained unexplained. In the work described in the present paper, we investigated two possible kinds of explanation for this phenomenon: namely that the extensive polydispersity results from a biological mechanism or that it is artifactual in origin. The data obtained, as a result of improving the purification and blotting methods, allowed us to show that in all of the tissues analyzed, each of the genes, MUC2–6, expresses mRNAs that are stable and are of an unusually large size to be found in eukaryotes (14–24 kilobases). Moreover, allelic variations in length of these mucin transcripts were observed. We demonstrate that these variations are directly related to the variable number of tandem repeat polymorphisms seen at the DNA level.
Surinder K. Batra - One of the best experts on this subject based on the ideXlab platform.
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mucins in the pathogenesis of breast cancer implications in diagnosis prognosis and therapy
Biochimica et Biophysica Acta, 2011Co-Authors: Partha Mukhopadhyay, Maneesh Jain, Surinder K. Batra, Subhankar Chakraborty, Moorthy P Ponnusamy, Imayavaramban LakshmananAbstract:Abstract Mucins are high molecular weight, multifunctional glycoproteins comprised of two structural classes—the large transmembrane mucins and the gel-forming or secreted mucins. The primary function of mucins is to protect and lubricate the luminal surfaces of epithelium-lined ducts in the human body. Recent studies have identified a differential expression of both membrane bound (MUC1, MUC4 and MUC16) and secreted mucins (MUC2, MUC5AC, MUC5B and MUC6) in breast cancer tissues when compared with the non-neoplastic breast tissues. Functional studies have also uncovered many unique roles of mucins during the progression of breast cancer, which include modulation in proliferative, invasive and metastatic potential of tumor cells. Mucins function through many unique domains that can form complex association with various signaling molecules including growth factor receptors and intercellular adhesion molecules. While there is growing information about mucins in various malignancies including breast cancer, no focused review is there on the expression and functional roles of mucins in breast cancer. In this present review, we have discussed the differential expression and functional roles of mucins in breast cancer. The potential of mucins as diagnostic and prognostic markers and as therapeutic targets in breast cancer have also been discussed.
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mucin muc gene expression in human pancreatic adenocarcinoma and chronic pancreatitis a potential role of muc4 as a tumor marker of diagnostic significance
Clinical Cancer Research, 2001Co-Authors: Mahefatiana Andrianifahanana, Nicolas Moniaux, Michael A Hollingsworth, Jean-pierre Aubert, Bruno M Schmied, Jorg Ringel, Helmut Friess, Markus W Buchler, Surinder K. BatraAbstract:Purpose: Mucins are important biomolecules that frequently display an altered expression under pathological conditions. In a search for a unique and reliable marker(s) specific for pancreatic adenocarcinoma, we investigated the expression of different MUC genes in pancreatic tumors and tumor cell lines, in chronic pancreatitis, and in the normal pancreas. Experimental Design: Total RNA from 16 pancreatic tumors, 10 chronic pancreatitis tissues, 7 normal pancreas tissues, and 15 pancreatic tumor cell lines were analyzed by reverse transcription-PCR with primers specific for MUC1 , MUC2 , MUC3 , MUC4 , MUC5AC , MUC5B , MUC6 , and MUC7 genes and by RNA slot blot analyses. Results: Our results revealed that of all of the mucins examined, only MUC4 displayed a differential expression that was specific for pancreatic adenocarcinoma. Indeed, a substantial number of tumor tissue samples (12 of 16) and tumor cell lines (11 of 15) expressed MUC4 mRNA, whereas samples from chronic pancreatitis (0 of 10) and the normal pancreas (0 of 7) tissues failed to exhibit any detectable level of this mucin. In contrast, no significant alteration was observed in the expression of the other mucins relative to that in the normal pancreas samples. Conclusions: Overall, this work demonstrates that pancreatic mucin MUC4 is a tumor-associated mucin. Furthermore, the present study introduces a novel avenue to discriminate between pancreatic adenocarcinoma and pancreatitis. Future investigations of the role played by MUC4 in pancreatic adenocarcinoma may prove to be useful in the formulation of strategies for the diagnosis and therapeutic treatment of this malignancy.
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structural organization and classification of the human mucin genes
Frontiers in Bioscience, 2001Co-Authors: Nicolas Moniaux, Nicole Porchet, Fabienne Escande, J P Aubert, Surinder K. BatraAbstract: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.
Michael R Knowles - One of the best experts on this subject based on the ideXlab platform.
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meconium ileus in cystic fibrosis is not linked to central repetitive region length variation in muc1 muc2 and muc5ac
Journal of Cystic Fibrosis, 2014Co-Authors: Xue Liang Guo, Rhonda G Pace, Jaclyn R Stonebraker, Wanda K Oneal, Michael R KnowlesAbstract:Background Mucins are excellent candidates for contributing to the presence of meconium ileus (MI) in cystic fibrosis (CF) due to their extensive genetic variation and known function in intestinal physiology. The length of variants in mucin central repetitive regions has not been explored as “risk” factors for MI in CF.
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short communication meconium ileus in cystic fibrosis is not linked to central repetitive region length variation in muc1 muc2 and muc5ac
2014Co-Authors: Xue Liang Guo, Rhonda G Pace, Jaclyn R Stonebraker, Wanda K Oneal, Michael R KnowlesAbstract:Background: Mucins are excellent candidates for contributing to the presence of meconium ileus (MI) in cystic fibrosis (CF) due to their extensive genetic variation and known function in intestinal physiology. The length of variants in mucin central repetitive regions has not been explored as “risk” factors for MI in CF. Methods: We investigated the length polymorphisms in the central repetitive regions of MUC1, MUC2, and MUC5AC by Southern blot and tested for association with MI in CF subjects. Results: No significant associations were found for the allele sizes of any of the genes with respect to the prevalence of MI (p values = 0.33, 0.16, and 0.71 for MUC1, MUC2, and MUC5AC, respectively). Conclusions: The genetic length variants in the central repetitive region of three MUC genes studied are not associated with MI in subjects with CF.
Mark A Jenkins - One of the best experts on this subject based on the ideXlab platform.
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Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype
Modern Pathology, 2013Co-Authors: Michael D Walsh, Mark Clendenning, Sallyann Pearson, Rhiannon J Walters, Belinda Nagler, David Packenas, John L Hopper, Mark A Jenkins, Elizabeth Williamson, Andrew M HaydonAbstract:Mucinous differentiation is associated with both CpG island methylator phenotype and microsatellite instability in colorectal cancer. The mucinous phenotype derives from abundant expression of the colonic goblet cell mucin, MUC2, and de novo expression of gastric foveolar mucin, MUC5AC. We, therefore, investigated the protein expression levels of MUC2 and MUC5AC, as well as MUC5B and MUC6, in molecular subtypes of colorectal cancer. Seven-hundred and twenty-two incident colorectal carcinomas occurring in 702 participants of the Melbourne Collaborative Cohort Study were characterized for methylator status, MLH1 methylation, somatic BRAF and KRAS mutations, microsatellite-instability status, MLH1, MSH2, MSH6, and PMS2 mismatch repair, and p53 protein expression, and their histopathology was reviewed. Protein expression levels of MUC2, MUC5AC, MUC5B, MUC6, and the putative mucin regulator CDX2 were compared with molecular and clinicopathological features of colorectal cancers using odds ratios and corresponding 95% confidence intervals. MUC2 overexpression (>25% positive tumor cells) was observed in 33% colorectal cancers, MUC5B expression in 53%, and de novo MUC5AC and MUC6 expression in 50% and 39%, respectively. Co-expression of two or more of the mucins was commonly observed. Expression of MUC2, MUC5AC and MUC6 was strongly associated with features associated with tumorigenesis via the serrated neoplasia pathway, including methylator positivity, somatic BRAF p.V600E mutation, and mismatch repair deficiency, as well as proximal location, poor differentiation, lymphocytic response, and increased T stage (all P
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expression of muc2 muc5ac muc5b and muc6 mucins in colorectal cancers and their association with the cpg island methylator phenotype
Modern Pathology, 2013Co-Authors: Michael Walsh, Mark Clendenning, Elizabeth A Williamson, Sallyann Pearson, Rhiannon J Walters, Belinda Nagler, David Packenas, Aung Ko Win, John L Hopper, Mark A JenkinsAbstract:Mucinous differentiation is associated with both CpG island methylator phenotype and microsatellite instability in colorectal cancer. The mucinous phenotype derives from abundant expression of the colonic goblet cell mucin, MUC2, and de novo expression of gastric foveolar mucin, MUC5AC. We, therefore, investigated the protein expression levels of MUC2 and MUC5AC, as well as MUC5B and MUC6, in molecular subtypes of colorectal cancer. Seven-hundred and twenty-two incident colorectal carcinomas occurring in 702 participants of the Melbourne Collaborative Cohort Study were characterized for methylator status, MLH1 methylation, somatic BRAF and KRAS mutations, microsatellite-instability status, MLH1, MSH2, MSH6, and PMS2 mismatch repair, and p53 protein expression, and their histopathology was reviewed. Protein expression levels of MUC2, MUC5AC, MUC5B, MUC6, and the putative mucin regulator CDX2 were compared with molecular and clinicopathological features of colorectal cancers using odds ratios and corresponding 95% confidence intervals. MUC2 overexpression (>25% positive tumor cells) was observed in 33% colorectal cancers, MUC5B expression in 53%, and de novo MUC5AC and MUC6 expression in 50% and 39%, respectively. Co-expression of two or more of the mucins was commonly observed. Expression of MUC2, MUC5AC and MUC6 was strongly associated with features associated with tumorigenesis via the serrated neoplasia pathway, including methylator positivity, somatic BRAF p.V600E mutation, and mismatch repair deficiency, as well as proximal location, poor differentiation, lymphocytic response, and increased T stage (all P<0.001). Overexpression was observed in tumors with and without mucinous differentiation. There were inverse associations between expression of all four mucins and p53 overexpression. CDX2 expression was inversely associated with MUC2, MUC5AC and MUC6 expression. Our results suggest that, in methylator-positive tumors, mucin genes on chromosome 11p15.5 region undergo increased expression via mechanisms other than direct regulation by CDX2.
Jean-pierre Aubert - One of the best experts on this subject based on the ideXlab platform.
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mucin muc gene expression in human pancreatic adenocarcinoma and chronic pancreatitis a potential role of muc4 as a tumor marker of diagnostic significance
Clinical Cancer Research, 2001Co-Authors: Mahefatiana Andrianifahanana, Nicolas Moniaux, Michael A Hollingsworth, Jean-pierre Aubert, Bruno M Schmied, Jorg Ringel, Helmut Friess, Markus W Buchler, Surinder K. BatraAbstract:Purpose: Mucins are important biomolecules that frequently display an altered expression under pathological conditions. In a search for a unique and reliable marker(s) specific for pancreatic adenocarcinoma, we investigated the expression of different MUC genes in pancreatic tumors and tumor cell lines, in chronic pancreatitis, and in the normal pancreas. Experimental Design: Total RNA from 16 pancreatic tumors, 10 chronic pancreatitis tissues, 7 normal pancreas tissues, and 15 pancreatic tumor cell lines were analyzed by reverse transcription-PCR with primers specific for MUC1 , MUC2 , MUC3 , MUC4 , MUC5AC , MUC5B , MUC6 , and MUC7 genes and by RNA slot blot analyses. Results: Our results revealed that of all of the mucins examined, only MUC4 displayed a differential expression that was specific for pancreatic adenocarcinoma. Indeed, a substantial number of tumor tissue samples (12 of 16) and tumor cell lines (11 of 15) expressed MUC4 mRNA, whereas samples from chronic pancreatitis (0 of 10) and the normal pancreas (0 of 7) tissues failed to exhibit any detectable level of this mucin. In contrast, no significant alteration was observed in the expression of the other mucins relative to that in the normal pancreas samples. Conclusions: Overall, this work demonstrates that pancreatic mucin MUC4 is a tumor-associated mucin. Furthermore, the present study introduces a novel avenue to discriminate between pancreatic adenocarcinoma and pancreatitis. Future investigations of the role played by MUC4 in pancreatic adenocarcinoma may prove to be useful in the formulation of strategies for the diagnosis and therapeutic treatment of this malignancy.
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developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands i stomach a relationship to gastric carcinoma
Journal of Histochemistry and Cytochemistry, 2000Co-Authors: Marie-pierre Buisine, Nicole Porchet, Jean-pierre Aubert, Mariechristine Copin, L Devisme, V Maunoury, Elisabeth Deschodt, Bernard GosselinAbstract:Studies were undertaken to provide information regarding cell-specific expression of mucin genes in stomach and their relation to developmental and neoplastic patterns of epithelial cytodifferentiation. In situ hybridization was used to study mRNA expression of eight mucin genes (MUC1-4, MUC5AC, MUC5B, MUC6, MUC7) in stomach of 13 human embryos and fetuses (8-27 weeks' gestation), comparing these with normal, metaplastic, and neoplastic adult tissues. These investigations have demonstrated that MUC1, MUC4, MUC5AC, MUC5B, and MUC6 are already expressed in the embryonic stomach at 8 weeks of gestation. MUC3 mRNA expression can be observed from 10.5 weeks of gestation. MUC2 is expressed at later stages, concomitant with mucous gland cytodifferentiation. Normal adult stomach is characterized by strong expression of MUC1, MUC5AC, and MUC6, less prominent MUC2, and sporadic MUC3 and MUC4, without MUC5B and MUC7. Intestinal metaplasia is characterized by an intestinal-type pattern with MUC2 and MUC3 mRNA expression. Gastric carcinomas exhibit altered mucin gene expression patterns with disappearance of MUC5AC and MUC6 mRNAs in some tumor glands, abnormal expression of MUC2, and reappearance of MUC5B mRNAs. In conclusion, we have observed that patterns of mucin gene expression in embryonic and fetal stomach could show similarities with some gastric carcinomas in adults. Differences in mucin gene expression in developmental, metaplastic, and neoplastic stomach compared to normal adult stomach suggest a possible regulatory role for their products in gastric epithelial cell proliferation and differentiation.
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transdermal nicotine decreases mucosal il 8 expression but has no effect on mucin gene expression in ulcerative colitis
Inflammatory Bowel Diseases, 1998Co-Authors: Beatrice Louvet, Nicole Porchet, Marie-pierre Buisine, Jean-pierre Aubert, Pierre Desreumaux, William J Tremaine, Monique Capron, Antoine Cortot, Jeanfrederic Colombel, William J SandbornAbstract:Abstract Our goal was to determine the effect of transdermal nicotine on cytokine and mucin gene transcription in ulcerative colitis (UC). Sixty-four nonsmoking patients with active UC were randomly assigned to transdermal nicotine (maximum dose 22 mg/day) or placebo for 4 weeks. Clinical assessment and colonic mucosal biopsies were obtained at entry and after 4 weeks. Inflammatory and immunoregulatory cytokines were assessed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR). Based on this initial screen. IL-8 mRNA levels were measured by RT-competitive PCR. MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 mRNA concentrations were measured by quantitative dot blot analysis. Cytokine mRNA expression, except for IL-8, was similar in all patients. IL-8 mRNA levels were significantly decreased in the colonic mucosa of nicotine-treated patients who improved (p = 0.04). IL-8 mRNA values were similar before and after treatment in nonresponding nicotine-treated patients and in all placebo-treated patients. Mucin gene expression was similar in all patient groups. Beneficial effects of transdermal nicotine in active UC may result from decrease of IL-8 expression at the transcriptional level. Transdermal nicotine has no effect on mucin gene transcription.
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human mucin genes muc2 muc3 muc4 muc5ac muc5b and muc6 express stable and extremely large mrnas and exhibit a variable length polymorphism an improved method to analyze large mrnas
Journal of Biological Chemistry, 1998Co-Authors: Virginie Debailleul, Jean-pierre Aubert, Anne Laine, Guillemette Huet, Pascal Mathon, Maud Collyn Dhooghe, Nicole PorchetAbstract:Abstract Of the nine mucin genes that have been characterized, only MUC1 and MUC7 have been fully sequenced, and their transcripts can be detected as distinct bands of predicted size by Northern blot analysis. In contrast, the RNA patterns observed for each of the other MUC genes have usually shown a very high degree of polydispersity. This polydispersity has been believed to be one of the typical features of the mucin mRNAs, but until now, its origin has remained unexplained. In the work described in the present paper, we investigated two possible kinds of explanation for this phenomenon: namely that the extensive polydispersity results from a biological mechanism or that it is artifactual in origin. The data obtained, as a result of improving the purification and blotting methods, allowed us to show that in all of the tissues analyzed, each of the genes, MUC2–6, expresses mRNAs that are stable and are of an unusually large size to be found in eukaryotes (14–24 kilobases). Moreover, allelic variations in length of these mucin transcripts were observed. We demonstrate that these variations are directly related to the variable number of tandem repeat polymorphisms seen at the DNA level.