Altered expression of MUC2, MUC4, and MUC5 mucin genes in pancreas tissues and cancer cell lines

Balagué, Cristina; Gambús, Gemma; Carrato, Cristina; Porchet, Nicole; Aubert, Jean‐Pierre; Kim, Young S.; Real, Francisco X.

doi:10.1016/0016-5085(94)90767-6

Cited by 155 publications

(119 citation statements)

References 31 publications

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“…The overexpression of MUC1 is observed during the early stages of the development of PC, which is further increased in invasive carcinoma (Levi et al, 2004). On the other hand, MUC4 is minimally or not expressed in the normal pancreas or chronic pancreatitis but is highly expressed in human pancreatic tumours and pancreatic tumour cell lines (Balague et al, 1994;Choudhury et al, 2000;Andrianifahanana et al, 2001).…”

Section: Abnormal Expression Of Mucin Genes In Pcmentioning

confidence: 99%

Multiple roles of mucins in pancreatic cancer, a lethal and challenging malignancy

et al. 2004

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Mucins are members of an expanding family of large multifunctional glycoproteins. Pancreatic mucins have important biological functions, including the protection, lubrication, and moisturisation of the surfaces of epithelial tissues lining ductal structures within the pancreas. Several lines of evidence support the notion that deregulated mucin production is a hallmark of inflammatory and neoplastic disorders of the pancreas. Herein, we discuss the factors that contribute to the lethality of pancreatic cancer as well as the key role played by mucins, particularly MUC1 and MUC4, in the development and progression of the disease. Aspects pertaining to the aberrant expression and glycosylation of mucins are discussed, with special emphasis on their potential impact on the design and implementation of adequate diagnostic and therapeutic strategies for combating this lethal malignancy.

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Section: Abnormal Expression Of Mucin Genes In Pcmentioning

confidence: 99%

Multiple roles of mucins in pancreatic cancer, a lethal and challenging malignancy

et al. 2004

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“…MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines; however, its expression is undetectable in the normal pancreas or chronic pancreatitis (Balague et al, 1994;Hollingsworth et al, 1994;Choudhury et al, 2000a;Andrianifahanana et al, 2001). MUC4 is expressed by metaplastic ducts and its expression increases with increasing grade in pancreatic intraepithelial neoplasias (Swart et al, 2002;Park et al, 2003).…”

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confidence: 99%

Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells

et al. 2007

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MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4a, and a membrane-bound growth factor-like subunit, MUC4b. MUC4 mRNA contains unique 5 0 and 3 0 coding sequences along with a large variable number of tandem repeat (VNTR) domain of 7 -19 kb. A direct association of MUC4 overexpression has been established with the degree of invasiveness and poor prognosis of pancreatic cancer.To understand the precise role of MUC4 in pancreatic cancer, we engineered a MUC4 complementary DNA construct, mini-MUC4, whose deduced protein (320 kDa) is comparable with that of wild-type MUC4 (930 kDa) but represents only 10% of VNTR. Stable ectopic expression of mini-MUC4 in two human pancreatic cancer cell lines, Panc1 and MiaPaCa, showed that MUC4 minigene expression follows a biosynthesis and localisation pattern similar to the wild-type MUC4. Expression of MUC4 resulted in increased growth, motility, and invasiveness of the pancreatic cancer cells in vitro. Ultra-structural examination of MUC4-transfected cells showed the presence of increased number and size of mitochondria. The MUC4-expressing cells also demonstrated an enhanced tumorigenicity in an orthotopic xenograft nude mice model, further supporting a direct role of MUC4 in inducing the cancer properties. In conclusion, our results suggest that MUC4 promotes tumorigenicity and is directly involved in growth and survival of the cancer cells.

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“…MUC5B is expressed mainly in bronchus glands and also in submaxillary glands, endocervix, gall bladder, and pancreas (31)(32)(33)(34)(35). The structural organization of the peptide deduced from the nucleotide sequence of the central region of MUC5B has been published recently (30).…”

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Genomic Organization of the 3′ Region of the Human Mucin GeneMUC5B

Desseyn¹,

Aubert²,

Seuningen³

et al. 1997

Journal of Biological Chemistry

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115

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MUC5B, mapped clustered with MUC6, MUC2, and MUC5AC to chromosome 11p15.5, is a human mucin gene of which the genomic organization is being elucidated. We have recently published the sequence and the peptide organization of its huge central exon, 10,713 base pairs (bp) in length. We present here the genomic organization of its 3 region, which encompasses 10,690 bp. The genomic sequence has been completely determined. The 3 region of MUC5B is composed of 18 exons ranging in size from 32 to 781 bp, contrasting thus with the very large central exon. The sizes of the 18 introns range from 114 to 1118 bp. Some repetitive sequences were identified in four introns. The peptide deduced from the sequence of the 18 exons consists of an 808-amino acid peptide. This carboxyl-terminal region exhibits extensive sequence similarity to MUC2, MUC5AC, and von Willebrand factor, particularly the number and the positions of the cysteine residues, suggesting that this domain may be derived from a common ancestral gene. The presence in these components of a cystine knot also found in growth factors such as transforming growth factor-␤ is of particular interest. Moreover, one part of this peptide is identical to the 196-amino acid sequence deduced from the cDNA clone pSM2-1, which codes for a part of the high molecular weight mucin MG1 isolated from human sublingual gland. Considering the expression pattern of MUC5B and the origin of MG1, we can thus conclude that MUC5B encodes MG1.Mucus is the layer that covers, protects, and lubricates the luminal surfaces of epithelial respiratory, gastrointestinal, and reproductive tracts. These basic properties are due to the viscous and viscoelastic properties of mucins, the major glycoprotein components of mucus. Mucins constitute a family of high molecular mass glycoproteins synthesized by the goblet cells of the epithelia and in some cases by submucosal glands (for more complete reviews, see Refs. 1-3).Alterations of the biosynthesis of mucins affecting the protein core and/or the carbohydrate content linked to the peptide have been observed in numerous pathological situations such as various adenomas and carcinomas, inflammatory diseases such as cystic fibrosis, asthma, chronic bronchitis, or inflammatory bowel diseases (4 -7). Moreover, the hypersecretion of mucins and the presence of alternating hydrophobic and hydrophilic domains in mucins have been shown to play a central role in the pathogenesis of cholesterol gallstones (8, 9).All apomucins contain tandemly repeated sequences rich in threonine and/or serine. Due to the high carbohydrate content, the peptide moiety of mucins has been difficult to characterize. cDNA cloning has enabled researchers to approach the study of the mucins over the past decade. Today, the membrane-associated mucin MUC1 and the secreted MUC7 are the only mucins for which the full-length cDNA and the genomic organization have been reported (10 -13). Both were revealed to be, in fact, small mucins. A complete cDNA of the large secreted mucin MUC2 (14 -17) has been...

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Altered expression of MUC2, MUC4, and MUC5 mucin genes in pancreas tissues and cancer cell lines

Cited by 155 publications

References 31 publications

Multiple roles of mucins in pancreatic cancer, a lethal and challenging malignancy

Multiple roles of mucins in pancreatic cancer, a lethal and challenging malignancy

Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells

Genomic Organization of the 3′ Region of the Human Mucin GeneMUC5B

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