Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

MUC4 (mucin 4, cell surface associated)

Identity

Other namessv0-MUC4
HGNC (Hugo) MUC4
LocusID (NCBI) 4585
Location 3q29
Location_base_pair Starts at 195473638 and ends at 195538844 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note MUC4 belongs to the human mucin family, and more specifically to the subgroup of the membrane-anchored mucin. It is an O-glycoprotein that can extend up to 2 micrometer over the cell membrane. It is suggested that MUC4 is translated as a single precursor polypeptide, which is further cleaved at a GDPH site in two subunits, MUC4a and MUC4b. MUC4a is the mucin type subunit and MUC4b is the membrane-bound growth factor like subunit. Both subunits remain non-covalently associated. MUC4 is also found in several secretions such as in the milk. MUC4 along with other mucins is part of the mucus, the viscous gel that covers, moisturizes, and protects all epithelial surfaces.

DNA/RNA

Note MUC4 gene is located on the chromosome 3 in the region q29, oriented from telomere to centromere and clustered with another mucin gene MUC20. MUC4 is highly polymorphic, harboring numerous sequences repeated in tandem and presenting variable number of tandem repeat (VNTR) polymorphism. The sequence repeated in tandem is localized in exon 2 and is composed of a 48 bp repetitive unit. Due to this highly variable region 27 distinct alleles have been identified for MUC4. Among these, three alleles represent 78.6% of all alleles detected: the 19 kb, 10.5 kb, and 15 kb that present a prevalence of 47%, 18%, and 13.6 % respectively. In addition, 24 alternatively splice transcripts have been identified for MUC4 gene, coding for membrane-anchored and secreted forms.
 
  A: Schematic representation of MUC4 gene and mRNA. The representation is not drawn to scale.
B: Example of VTNR polymorphism associated with MUC4 gene. The gDNA of 18 healthy individuals was extracted from the PBMCs and digested by ECORI and PstI endonucleases. Southern blot was hybridized with [32] P-radiolabeled probes of each sequence repeated in tandem.
Description MUC4 gene spans on a 70 kb-long DNA fragment located in 3q29 at the position 196959310-197023545. This position varies from individual to individual due to VNTR polymorphism of several sequences repeated in tandem. The largest domain repeated in tandem is localized in exon 2 and is composed of a motif of 48 bp, repeated up to 400 times. This domain varies from 7 to 19 kb. Three other sequences repeated in tandem with a motif of 15 bp, 26 to 32 bp and 32 bp are positioned in introns 3, 4, and 5 respectively. Theses sequences present also VNTR polymorphism.
Various SNPs are reported for MUC4 coding sequence; however, either VNTR or SNP polymorphism have been associated with specific physiological condition or disease.
Transcription MUC4 is transcribed in at least 24 distinct splice variant forms in normal and malignant human tissues. Twenty-two of these variants are generated by alternative splicing of the exons at the 3'-extremity and are referred sv1- to sv21-MUC4. Two splice forms are generated by alternative splicing of exon 2 and are called MUC4/X and MUC4/Y. So far, it is unknown if these splice forms are translated, however their deduced amino acid composition leads to secreted and membrane-anchored proteins. The main isoform of MUC4 (up to 27.5 kb in size), referred to as sv0-MUC4, encodes for full-length MUC4 protein.
MUC4 5'-flanking region (over 3.7 kb upstream of the first ATG) has been characterized. Two transcriptionally active units drive MUC4 expression. The proximal promoter is TATA-less, possesses a transcription initiation site at -199, and is mainly composed of GC-rich domains that are potential binding sites for Sp1 and the CACCC box binding protein. Furthermore, a very high density of binding sites for factors known to initiate transcription in TATA-less promoters (Sp1, CACCC box, GRE, AP-1, PEA3 and Med-1) was found within that promoter. The distal promoter is flanked by a TATA box located at -2672/-2668 and three transcriptional initiation sites at -2603, -2604 and -2605. Responsive regions and cis-elements for transcription factors involved in Protein Kinase A, Protein Kinase C, cAMP signaling pathways, in inflammation (NF-kB) and in intestinal (HNF-1, HNF-3, HNF4A, GATA4, GATA-6, CDX1, CDX2) and respiratory ( TITF1, GATA-6, HNF-3b) epithelial cell differentiation have also been identified. Altogether, these results suggest that MUC4 transcription is complex, tightly regulated and involves many signaling pathways.

Protein

Note MUC4 is a high molecular weight O-glycoprotein. Molecular weight for precursor full-length MUC4 protein may range between 550-930 kDa depending upon the VNTR polymorphism. Classically, the protein moiety represents 20% of the mucin mature molecular weight, leading to a fully glycosylated protein of 4,650 kDa.
 
  A: Schematic representation of the modular structure of MUC4.
B: Schematic representation of MUC4 protein. The representation is not drawn to scale.
Description MUC4 is synthesized as a precursor cleaved in two subunits that remain non-covalently link to each other: the mucin type subunit MUC4a of 850 kDa and the membrane-bound growth factor like subunit MUC4b of 80 kDa. MUC4 is a modular protein, composed of very distinct domains.
MUC4a is rich in serine, threonine, and proline residues and present a central domain composed of 16 amino acids repeated in tandem up to 400 times. This repetitive domain is the hallmark of the mucin family. The carboxy-extremity of MUC4a harbors a NIDO and an AMOP domain. The NIDO domain is a domain identified in the nidogen protein and present in several proteins such as the tumor endothelial marker TEM7. TEM7 plays a role in angiogenesis via its NIDO domain. The AMOP domain (adhesion-associated domain in MUC4 and other proteins) is suggested to have a role in cell adhesion. In addition to the AMOP and NIDO domains, analysis of the MUC4a sequence reveals a high degree of similarity with a von Willebrand factor (vWF) D domain. However, none of the cysteine residues that characterized a vWF D domain are conserved in the MUC4 sequence.
The MUC4b subunit contains two domains rich in N-glycosylation sites, 3 EGF-like domains, a transmembrane sequence, and a small 22 amino acids long cytoplasmic tail.
Expression MUC4 expression is developmentally regulated. In normal physiologic conditions, MUC4 is expressed in the epithelium of the respiratory, digestive and urogenital tracts, with level that varies from tissue to tissues. In the respiratory tract, MUC4 is strongly expressed in the trachea and the lung. In the digestive tract, its main pattern of expression is the oesophagus and the colon. However, MUC4 is not expressed by the annex of the digestive tract such as the liver, the pancreas, and the gallbladder. MUC4 is also expressed by the epithelial cells of the ocular and auditory systems.
MUC4 is overexpressed or aberrantly expressed in several diseases, such as inflammatory bowel diseases (Crohn or ulcerative colitis) and malignancy. For instance, MUC4 is overexpressed in lung, oesophagus, and colon cancer and is aberrantly expressed in pancreatic cancer. Neoexpression of MUC4 is observed early in precancerous pancreatic intraepithelial neoplastic lesions that further correlates with the disease progression stages.
Many studies has been conducted on human pancreatic or other cancer cell lines in order to elucidate molecular mechanisms responsible for aberrant expression of MUC4 in diseased condition. Initial studies about MUC4 transcriptional regulation showed that Sp1 and Sp3 were important regulators of MUC4 basal expression. EGF and TGF-b growth factors and PKC signaling pathway stimulation results in up regulation of the promoter activity. Whereas TNF-a and IFN-g inflammatory cytokines alone had no effect on MUC4 transcriptional activity, a strong synergistic effect between IFN-g and TNF-a or IFN-g and TGF-b was observed. Activation by IFN-g was then showed to be mediated by STAT-1. More recently, Th1 (IL-2) and Th2 (IL-12, IL-10) cytokines were shown to interfere with pancreatic tumorigenic environment and possibly modulate MUC4 expression. Subsequent studies aimed at deciphering MUC4 regulation by TGF-b pathway showed that it could be either Smad4-dependent, Smad4-independent (MAPK, PKA, PKC). Retinoic acid induced MUC4 expression was mediated by TGF-b2 and involved RAR-a. TGF-b2 expression in vivo also correlated with that of MUC4 in pancreatic tumors. Interestingly, recent data have shown that MUC4 is negatively regulated by cystic fibrosis transmembrane regulator (CFTR), a chloride channel that is defective in CF.
In oesophageal cancer cells, MUC4 is regulated by bile acids via activation of phosphatidylinositol 3-kinase pathway or activation of HNF-1a.
Studies in lung adenocarcinoma cell lines focused on cytokines involved in airway inflammation showed that MUC4 is regulated by IL-4 via JAK-3 and IL-9.
Identification of the molecular mechanisms governing MUC4 expression will be very informative to assign direct roles to that mucin in carcinogenesis and on the biological properties of the tumor cell and should provide new tools in the future for therapeutic intervention.
Localisation In normal physiologic situation, MUC4 is localized in the membrane at the apical region of the cells and in the mucus secretion. During cancer development, MUC4 exhibits diffuse expression in both the membrane and cytoplasm. Furthermore, due to loss of cell polarity, defined apical localization of MUC4 is disrupted.
Function MUC4 transmembrane mucin is a highly glycosylated protein with an extended rigid extracellular domain that may confer a role for MUC4 as a molecular sensor between the extracellular milieu and the epithelial cell. MUC4 is also the putative ligand of ERBB2 oncogenic receptor and thus may participate in cell signalling, influence cell proliferation, tumor progression, tumor cell morphology, cell polarity and escape to immune surveillance. Moreover, its over-expression in numerous cancers (lung, oesophagus, intestine, pancreas, etc.) is often associated with a poor prognosis. Functional role of MUC4 in pancreatic tumor growth and metastasis has also been recently demonstrated.
MUC4 consists of two subunits, the extracellular highly glycosylated mucin subunit (MUC4-a) and a transmembrane subunit containing three EGF-like domains (MUC4-b). These subunits of MUC4 may confer diverse functions to MUC4. The large sized extracellular subunit may provide the anti-adhesive or adhesive functions. The anti-adhesive function of MUC4 may aid in loosening the tumor cell-ECM interactions and facilitating the dissemination of tumor cells. Whereas, the high degree of glycosylation present in tandem repeat domain of MUC4 mucin can help in the adhesion of tumor cells to secondary sites and hence promote metastasis.
Another important function provided by MUC4 mucin is modulation of HER-2/ERBB2 mediated signaling. MUC4, an interaction partner of the proto-oncogene HER2, induces its localization at the cell membrane and triggers the signaling pathways downstream to HER-2 activation. The consequences of such interactions and signaling activation lead to malignant transformation. Hence, dysregulation of MUC4 expression, a protective cell surface protein, may have deleterious effects. The association of MUC4 with ERBB2 involves its translocation from the basolateral toward the apical membrane and increasing the membrane stability. Regulation of MUC4 and ERBB2 by PEA3 transcription factor was found to be conversely correlated, stressing the fact that balance between MUC4 and ErbB2 will orientate the tumor cell toward either differentiation or proliferation.
Under normal physiological conditions, MUC4 provides protection, lubrication and moisturization to the epithelial surfaces by trapping the foreign particles and preventing their accessibility to the cells. Being expressed in fetus tissue before differentiation, MUC4 is also suggested to play role in morphogenic functions.
Homology Several orthologues of MUC4 are totally or partially characterized. Mouse (mMuc4) and rat (rMuc4 or SMC for sialomucin complex) are fully identified and present 60 to 70% homology with human MUC4. Mouse mMuc4 is localized on the chromosome 16. Partial cDNA sequences of porcine, chinchilla, monkey, and dog Muc4 were also recently identified.

Implicated in

Entity Pancreatic adenocarcinoma.
Disease Worldwide, pancreatic cancer is the eleventh most common cancer and the fourth leading cause of cancer related death among men and women. Pancreatic cancer presents a 5-years survival rate of 5%. The incidence and age-adjusted mortality rate are almost equal, underscoring the aggressive nature of the disease.
Prognosis The DU-PAN-2 antibody that recognizes a tumor-associated antigen carries by the MUC4 protein is in clinical used in Japan for diagnostic of pancreatic adenocarcinoma. MUC4 is aberrantly expressed by 80% of the adenocarnicoma of the pancreatic gland while not expressed in the normal pancreas or in pancreatitis. In addition, MUC4 is expressed early in the onset of pancreatic cancer, already detected in the pancreatic intraepithelial neoplasia (PanIN) of stage I.
Oncogenesis In in vivo model, MUC4 was shown to promote tumor progression and metastasis. On clinical sample, patients negative for MUC4 expression has a better prognosis and a longer life time.
  

External links

Nomenclature
HGNC (Hugo)MUC4   7514
Cards
AtlasMUC4ID41459ch3q29
Entrez_Gene (NCBI)MUC4  4585  mucin 4, cell surface associated
GeneCards (Weizmann)MUC4
Ensembl (Hinxton)ENSG00000145113 [Gene_View]  chr3:195473638-195538844 [Contig_View]  MUC4 [Vega]
ICGC DataPortalENSG00000145113
cBioPortalMUC4
AceView (NCBI)MUC4
Genatlas (Paris)MUC4
WikiGenes4585
SOURCE (Princeton)NM_004532 NM_018406 NM_138297 NM_138298 NM_138299
Genomic and cartography
GoldenPath (UCSC)MUC4  -  3q29   chr3:195473638-195538844 -  3q29   [Description]    (hg19-Feb_2009)
EnsemblMUC4 - 3q29 [CytoView]
Mapping of homologs : NCBIMUC4 [Mapview]
OMIM158372   
Gene and transcription
Genbank (Entrez)AF058803 AF058804 AF177925 AJ000281 AJ010901
RefSeq transcript (Entrez)NM_004532 NM_018406 NM_138297 NM_138298 NM_138299
RefSeq genomic (Entrez)AC_000135 NC_000003 NC_018914 NT_005612 NT_187532 NT_187649 NT_187678 NT_187688 NT_187689 NT_187690 NT_187691 NW_001838886 NW_004929312
Consensus coding sequences : CCDS (NCBI)MUC4
Cluster EST : UnigeneHs.369646 [ NCBI ]
CGAP (NCI)Hs.369646
Alternative Splicing : Fast-db (Paris)GSHG0022347
Alternative Splicing GalleryENSG00000145113
Gene ExpressionMUC4 [ NCBI-GEO ]     MUC4 [ SEEK ]   MUC4 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ99102 (Uniprot)
NextProtQ99102  [Medical]
With graphics : InterProQ99102
Splice isoforms : SwissVarQ99102 (Swissvar)
Domaine pattern : Prosite (Expaxy)AMOP (PS50856)    EGF_1 (PS00022)    EGF_3 (PS50026)    NIDO (PS51220)    VWFD (PS51233)   
Domains : Interpro (EBI)AMOP [organisation]   EG-like_dom [organisation]   Nidogen_extracell_dom [organisation]   VWF_type-D [organisation]  
Related proteins : CluSTrQ99102
Domain families : Pfam (Sanger)AMOP (PF03782)    NIDO (PF06119)    VWD (PF00094)   
Domain families : Pfam (NCBI)pfam03782    pfam06119    pfam00094   
Domain families : Smart (EMBL)EGF (SM00181)  NIDO (SM00539)  VWD (SM00216)  
DMDM Disease mutations4585
Blocks (Seattle)Q99102
Human Protein AtlasENSG00000145113 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ99102
HPRD11829
IPIIPI00302162   IPI00827758   IPI00797458   IPI00178316   IPI00302258   IPI00828047   IPI00827725   IPI00827768   IPI00479285   IPI00790855   IPI00827732   IPI00795577   IPI00828180   IPI00789419   IPI00926144   IPI00924619   IPI01014158   IPI00981844   IPI00791006   IPI01009222   IPI00975849   IPI00926393   IPI00947018   IPI00945891   IPI00945491   IPI00945250   
Protein Interaction databases
DIP (DOE-UCLA)Q99102
IntAct (EBI)Q99102
FunCoupENSG00000145113
BioGRIDMUC4
InParanoidQ99102
Interologous Interaction database Q99102
IntegromeDBMUC4
STRING (EMBL)MUC4
Ontologies - Pathways
Ontology : AmiGOErbB-2 class receptor binding  proteinaceous extracellular matrix  extracellular space  Golgi lumen  integral component of plasma membrane  cell-matrix adhesion  membrane  O-glycan processing  extracellular matrix constituent, lubricant activity  maintenance of gastrointestinal epithelium  post-translational protein modification  cellular protein metabolic process  extracellular vesicular exosome  
Ontology : EGO-EBIErbB-2 class receptor binding  proteinaceous extracellular matrix  extracellular space  Golgi lumen  integral component of plasma membrane  cell-matrix adhesion  membrane  O-glycan processing  extracellular matrix constituent, lubricant activity  maintenance of gastrointestinal epithelium  post-translational protein modification  cellular protein metabolic process  extracellular vesicular exosome  
Protein Interaction DatabaseMUC4
Wikipedia pathwaysMUC4
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)MUC4
snp3D : Map Gene to Disease4585
SNP (GeneSNP Utah)MUC4
SNP : HGBaseMUC4
Genetic variants : HAPMAPMUC4
Exome VariantMUC4
1000_GenomesMUC4 
ICGC programENSG00000145113 
Somatic Mutations in Cancer : COSMICMUC4 
CONAN: Copy Number AnalysisMUC4 
Mutations and Diseases : HGMDMUC4
Mutations and Diseases : intOGenMUC4
Genomic VariantsMUC4  MUC4 [DGVbeta]
dbVarMUC4
ClinVarMUC4
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM158372   
MedgenMUC4
GENETestsMUC4
Disease Genetic AssociationMUC4
Huge Navigator MUC4 [HugePedia]  MUC4 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneMUC4
Homology/Alignments : Family Browser (UCSC)MUC4
Phylogenetic Trees/Animal Genes : TreeFamMUC4
Chemical/Protein Interactions : CTD4585
Chemical/Pharm GKB GenePA31319
Clinical trialMUC4
Cancer Resource (Charite)ENSG00000145113
Other databases
Probes
Litterature
PubMed115 Pubmed reference(s) in Entrez
CoreMineMUC4
iHOPMUC4
OncoSearchMUC4

Bibliography

Mucin 4 (MUC4) gene: regional assignment (3q29) and RFLP analysis.
Gross MS, Guyonnet-Duperat V, Porchet N, Bernheim A, Aubert JP, Nguyen VC
Annales de genetique. 1992 ; 35 (1) : 21-26.
PMID 1351710
 
Mucin gene expression in human embryonic and fetal intestine.
Buisine MP, Devisme L, Savidge TC, Gespach C, Gosselin B, Porchet N, Aubert JP
Gut. 1998 ; 43 (4) : 519-524.
PMID 9824580
 
Human mucin gene MUC4: organization of its 5'-region and polymorphism of its central tandem repeat array.
Nollet S, Moniaux N, Maury J, Petitprez D, Degand P, Laine A, Porchet N, Aubert JP
The Biochemical journal. 1998 ; 332 ( Pt 3) : 739-748.
PMID 9620877
 
Developmental mucin gene expression in the human respiratory tract.
Buisine MP, Devisme L, Copin MC, Durand-Rˆ©ville M, Gosselin B, Aubert JP, Porchet N
American journal of respiratory cell and molecular biology. 1999 ; 20 (2) : 209-218.
PMID 9922211
 
MUC4 and MUC5B transcripts are the prevalent mucin messenger ribonucleic acids of the human endocervix.
Gipson IK, Spurr-Michaud S, Moccia R, Zhan Q, Toribara N, Ho SB, Gargiulo AR, Hill JA 3rd
Biology of reproduction. 1999 ; 60 (1) : 58-64.
PMID 9858486
 
Complete sequence of the human mucin MUC4: a putative cell membrane-associated mucin.
Moniaux N, Nollet S, Porchet N, Degand P, Laine A, Aubert JP
The Biochemical journal. 1999 ; 338 ( Pt 2) : 325-333.
PMID 10024507
 
Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. II. Duodenum and liver, gallbladder, and pancreas.
Buisine MP, Devisme L, Degand P, Dieu MC, Gosselin B, Copin MC, Aubert JP, Porchet N
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2000 ; 48 (12) : 1667-1676.
PMID 11101635
 
Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. I. Stomach. A relationship to gastric carcinoma.
Buisine MP, Devisme L, Maunoury V, Deschodt E, Gosselin B, Copin MC, Aubert JP, Porchet N
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2000 ; 48 (12) : 1657-1666.
PMID 11101634
 
Retinoic acid-dependent transforming growth factor-beta 2-mediated induction of MUC4 mucin expression in human pancreatic tumor cells follows retinoic acid receptor-alpha signaling pathway.
Choudhury A, Singh RK, Moniaux N, El-Metwally TH, Aubert JP, Batra SK
The Journal of biological chemistry. 2000 ; 275 (43) : 33929-33936.
PMID 10938282
 
Alternative splicing generates a family of putative secreted and membrane-associated MUC4 mucins.
Moniaux N, Escande F, Batra SK, Porchet N, Laine A, Aubert JP
European journal of biochemistry / FEBS. 2000 ; 267 (14) : 4536-4544.
PMID 10880978
 
Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance.
Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H, Hollingsworth MA, Bˆºchler MW, Aubert JP, Batra SK
Clinical cancer research : an official journal of the American Association for Cancer Research. 2001 ; 7 (12) : 4033-4040.
PMID 11751498
 
Alternate splicing at the 3'-end of the human pancreatic tumor-associated mucin MUC4 cDNA.
Choudhury A, Moniaux N, Ringel J, King J, Moore E, Aubert JP, Batra SK
Teratogenesis, carcinogenesis, and mutagenesis. 2001 ; 21 (1) : 83-96.
PMID 11135323
 
Characterization of human mucin gene MUC4 promoter: importance of growth factors and proinflammatory cytokines for its regulation in pancreatic cancer cells.
Perrais M, Pigny P, Ducourouble MP, Petitprez D, Porchet N, Aubert JP, Van Seuningen I
The Journal of biological chemistry. 2001 ; 276 (33) : 30923-30933.
PMID 11418607
 
Muc4/sialomucin complex, the intramembrane ErbB2 ligand, in cancer and epithelia: to protect and to survive.
Carraway KL, Perez A, Idris N, Jepson S, Arango M, Komatsu M, Haq B, Price-Schiavi SA, Zhang J, Carraway CA
Progress in nucleic acid research and molecular biology. 2002 ; 71 : 149-185.
PMID 12102554
 
Genomic organization of MUC4 mucin gene. Towards the characterization of splice variants.
Escande F, Lemaitre L, Moniaux N, Batra SK, Aubert JP, Buisine MP
European journal of biochemistry / FEBS. 2002 ; 269 (15) : 3637-3644.
PMID 12153560
 
MUC4 expression increases progressively in pancreatic intraepithelial neoplasia.
Swartz MJ, Batra SK, Varshney GC, Hollingsworth MA, Yeo CJ, Cameron JL, Wilentz RE, Hruban RH, Argani P
American journal of clinical pathology. 2002 ; 117 (5) : 791-796.
PMID 12090430
 
Aberrant expression of MUC3 and MUC4 membrane-associated mucins and sialyl Le(x) antigen in pancreatic intraepithelial neoplasia.
Park HU, Kim JW, Kim GE, Bae HI, Crawley SC, Yang SC, Gum JR Jr, Batra SK, Rousseau K, Swallow DM, Sleisenger MH, Kim YS
Pancreas. 2003 ; 26 (3) : e48-e54.
PMID 12657964
 
Muc4/sialomucin complex, the intramembrane ErbB2 ligand, translocates ErbB2 to the apical surface in polarized epithelial cells.
Ramsauer VP, Carraway CA, Salas PJ, Carraway KL
The Journal of biological chemistry. 2003 ; 278 (32) : 30142-30147.
PMID 12748185
 
MUC4 is increased in high grade intraepithelial neoplasia in Barrett's oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio.
Bax DA, Haringsma J, Einerhand AW, van Dekken H, Blok P, Siersema PD, Kuipers EJ, Kusters JG
Journal of clinical pathology. 2004 ; 57 (12) : 1267-1272.
PMID 15563666
 
MUC4 mucin expression in human pancreatic tumours is affected by organ environment: the possible role of TGFbeta2.
Choudhury A, Moniaux N, Ulrich AB, Schmied BM, Standop J, Pour PM, Gendler SJ, Hollingsworth MA, Aubert JP, Batra SK
British journal of cancer. 2004 ; 90 (3) : 657-664.
PMID 14760381
 
Mucins in cancer: protection and control of the cell surface.
Hollingsworth MA, Swanson BJ
Nature reviews. Cancer. 2004 ; 4 (1) : 45-60.
PMID 14681689
 
A role for human MUC4 mucin gene, the ErbB2 ligand, as a target of TGF-beta in pancreatic carcinogenesis.
Jonckheere N, Perrais M, Mariette C, Batra SK, Aubert JP, Pigny P, Van Seuningen I
Oncogene. 2004 ; 23 (34) : 5729-5738.
PMID 15184872
 
Transcriptional regulation of human mucin MUC4 by bile acids in oesophageal cancer cells is promoter-dependent and involves activation of the phosphatidylinositol 3-kinase signalling pathway.
Mariette C, Perrais M, Leteurtre E, Jonckheere N, Hˆ©mon B, Pigny P, Batra S, Aubert JP, Triboulet JP, Van Seuningen I
The Biochemical journal. 2004 ; 377 (Pt 3) : 701-708.
PMID 14583090
 
Multiple roles of mucins in pancreatic cancer, a lethal and challenging malignancy.
Moniaux N, Andrianifahanana M, Brand RE, Batra SK
British journal of cancer. 2004 ; 91 (9) : 1633-1638.
PMID 15494719
 
Generation and characterization of anti-MUC4 monoclonal antibodies reactive with normal and cancer cells in humans.
Moniaux N, Varshney GC, Chauhan SC, Copin MC, Jain M, Wittel UA, Andrianifahanana M, Aubert JP, Batra SK
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2004 ; 52 (2) : 253-261.
PMID 14729877
 
Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis.
Singh AP, Moniaux N, Chauhan SC, Meza JL, Batra SK
Cancer research. 2004 ; 64 (2) : 622-630.
PMID 14744777
 
Synergistic induction of the MUC4 mucin gene by interferon-gamma and retinoic acid in human pancreatic tumour cells involves a reprogramming of signalling pathways.
Andrianifahanana M, Agrawal A, Singh AP, Moniaux N, van Seuningen I, Aubert JP, Meza J, Batra SK
Oncogene. 2005 ; 24 (40) : 6143-6154.
PMID 16007204
 
MUC4-expressing pancreatic adenocarcinomas show elevated levels of both T1 and T2 cytokines: potential pathobiologic implications.
Andrianifahanana M, Chauhan SC, Choudhury A, Moniaux N, Brand RE, Sasson AA, Pour PM, Batra SK
The American journal of gastroenterology. 2006 ; 101 (10) : 2319-2329.
PMID 17032197
 
Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125).
Chauhan SC, Singh AP, Ruiz F, Johansson SL, Jain M, Smith LM, Moniaux N, Batra SK
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2006 ; 19 (10) : 1386-1394.
PMID 16880776
 
IL-9 modulated MUC4 gene and glycoprotein expression in airway epithelial cells.
Damera G, Xia B, Ancha HR, Sachdev GP
Bioscience reports. 2006 ; 26 (1) : 55-67.
PMID 16779668
 
Cognitive, emotional, and quality of life outcomes in patients with pulmonary arterial hypertension.
White J, Hopkins RO, Glissmeyer EW, Kitterman N, Elliott CG
Respiratory research. 2006 ; 7 : page 55.
PMID 16579853
 
The mucin Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3.
Funes M, Miller JK, Lai C, Carraway KL 3rd, Sweeney C
The Journal of biological chemistry. 2006 ; 281 (28) : 19310-19319.
PMID 16690615
 
Membrane mucin Muc4 induces density-dependent changes in ERK activation in mammary epithelial and tumor cells: role in reversal of contact inhibition.
Pino V, Ramsauer VP, Salas P, Carothers Carraway CA, Carraway KL
The Journal of biological chemistry. 2006 ; 281 (39) : 29411-29420.
PMID 16891313
 
Muc4-ErbB2 complex formation and signaling in polarized CACO-2 epithelial cells indicate that Muc4 acts as an unorthodox ligand for ErbB2.
Ramsauer VP, Pino V, Farooq A, Carothers Carraway CA, Salas PJ, Carraway KL
Molecular biology of the cell. 2006 ; 17 (7) : 2931-2941.
PMID 16624867
 
Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas.
Singh AP, Chauhan SC, Bafna S, Johansson SL, Smith LM, Moniaux N, Lin MF, Batra SK
The Prostate. 2006 ; 66 (4) : 421-429.
PMID 16302265
 
Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy.
Singh AP, Chaturvedi P, Batra SK
Cancer research. 2007 ; 67 (2) : 433-436.
PMID 17234748
 
MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms.
Singh AP, Chauhan SC, Andrianifahanana M, Moniaux N, Meza JL, Copin MC, van Seuningen I, Hollingsworth MA, Aubert JP, Batra SK
Oncogene. 2007 ; 26 (1) : 30-41.
PMID 16799633
 
Regulation of the human mucin MUC4 by taurodeoxycholic and taurochenodeoxycholic bile acids in oesophageal cancer cells is mediated by hepatocyte nuclear factor 1alpha.
Piessen G, Jonckheere N, Vincent A, Hˆ©mon B, Ducourouble MP, Copin MC, Mariette C, Van Seuningen I
The Biochemical journal. 2007 ; 402 (1) : 81-91.
PMID 17037983
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written02-2007Nicolas Moniaux, Pallavi Chaturvedi, Isabelle Van Seuningen, Nicole Porchet, Ajay P. Singh, Surinder K. Batra

Citation

This paper should be referenced as such :
Moniaux, N ; Chaturvedi, P ; Van, Seuningen I ; Porchet, N ; Singh, AP ; Batra, SK
MUC4 (mucin 4, cell surface associated)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):201-206.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/MUC4ID41459ch3q29.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Aug 26 15:23:47 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.