Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucinous carcinomas are defined on the basis of the amount of the mucus component in the tumour mass. Apart from this quantitative criterion, a number of clinicopathological parameters (such as localisation, prevalence in different countries and age groups, association with HNPCC and inflammatory processes) and genetic alterations (e.g. frequency of mutation in Ki-ras and p53 genes, level of MUC2 expression) differentiate these tumours from the non-mucinous ones. Since a different set of genetic lesions implies different inducing agents, these observations suggest that there may be a 'mucinous pathway of carcinogenesis'. Further identification of genetic changes characteristic of the mucinous phenotype will help to understand the aetiology of these tumours and possibly establish markers for detection of the high-risk group.
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PMID:Is mucinous carcinoma of the colorectum a distinct genetic entity? 851 44

Previous histochemical studies have shown that changes occur in the composition of mucins both in preneoplastic and neoplastic lesions of the gastric mucosa. Since monoclonal antibodies are now available which recognize the protein product of distinct mucin genes, they are likely to provide useful tools for evaluating these changes. Thus, a monoclonal antibody 996/1 raised against a peptide epitope of the colonic mucin MUC2 was examined for its potential as a prognostic indicator in gastric cancer. 996/1 works well on formalin-fixed paraffin sections and shows good staining of the colonic goblet cells in the region of the golgi, while there is no staining of normal control gastric mucosa. The epitope was detected in all cases of intestinal metaplasia (44 samples) and some but not all cases of dysplasia (26 samples) and gastric carcinoma (74 samples). There was no significant difference between the positivity of the tumours according to their classification, stage and lymph node status. These results unfortunately gave little indication that this antibody would be a useful prognostic tool in gastric cancer. However, the pattern of 996/1 staining provides useful information about the molecular changes in mucin expression that occur in gastric carcinogenesis.
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PMID:Expression of a peptide epitope of the colonic mucin MUC2 in precursor lesions to gastric carcinoma. 889 66

To date, seven apomucins have been characterized and their expression in malignant and premalignant lesions is under evaluation. In this study, we examined the expression of MUC1, MUC2, MUC3, and MUC5/6 apomucins in cholangiocarcinoma (CC) and biliary epithelial dysplasia. We used 14 liver samples from patients with hepatolithiasis and CC, 11 with hepatolithiasis showing biliary epithelial dysplasia, 31 with CC alone (19 hilar, 10 peripheral, and 2 unclassifiable), and 14 with combined hepatocellular-cholangiocellular carcinoma (HC-CC) and immunohistochemically characterized the expression profiles of apomucins. Nondysplastic biliary epithelial cells in the intrahepatic large bile ducts constantly expressed MUC3 apomucin. MUC5/6 and MUC3 apomucin expression was widespread in dysplastic biliary epithelial cells in hepatolithiasis, although the latter was reduced or absent in dysplastic foci. CC extensively expressed MUC1 apomucin and focally expressed MUC2 apomucin. In addition, CC of the hilar type, including those with hepatolithiasis, frequently expressed MUC3 apomucin (68% and 57%, respectively), whereas those of the peripheral type infrequently expressed MUC3 apomucin (10%) (P < .01). MUC5/6 apomucin was more frequently expressed in well-differentiated (89%), compared with poorly differentiated CC (42%) (P < .01). Cholangiocellular elements of combined HC-CC frequently expressed MUC1 apomucin, although they rarely expressed MUC2 and MUC3 apomucin and infrequently expressed MUC5/6 apomucin. The frequent and aberrant expression of "gastric type" MUC5/6 apomucin in biliary epithelial dysplasia, as well as in CC, suggests that biliary epithelial cells gain a gastric apomucin phenotype during carcinogenesis. MUC3 apomucin expression in CC is a marker that suggests that CC arises in the intrahepatic large bile ducts.
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PMID:Characterization of apomucin expression in intrahepatic cholangiocarcinomas and their precursor lesions: an immunohistochemical study. 890 78

Mucins are high molecular weight glycoproteins that are heavily glycosylated with many oligosaccharide side chains linked O-glycosidically to the protein backbone. With the recent application of molecular biological methods, the structures of apomucins and regulation of mucin genes are beginning to be understood. At least nine human mucin genes have been identified to date. Although a complete protein sequence is known for only three human mucins (MUC1, MUC2, and MUC7), common motifs have been identified in many mucins. The pattern of tissue and cell-specific expression of these mucin genes are emerging, suggesting a distinct role for each member of this diverse mucin gene family. In epithelial cancers, many of the phenotypic markers for pre-malignant and malignant cells have been found on the carbohydrate and peptide moieties of mucin glycoproteins. The expression of carbohydrate antigens appears to be due to modification of peripheral carbohydrate structures and the exposure of inner core region carbohydrates. The expression of some of the sialylated carbohydrate antigens appears to correlate with poor prognosis and increased metastatic potential in some cancers. The exposure of peptide backbone structures of mucin glycoproteins in malignancies appears to be due to abnormal glycosylation during biosynthesis. Dysregulation of tissue and cell-specific expression of mucin genes also occurs in epithelial cancers. At present, the role of mucin glycoproteins in various stages of epithelial cell carcinogenesis (including the preneoplastic state and metastasis), in cancer diagnosis and immunotherapy is under investigation.
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PMID:Mucin glycoproteins in neoplasia. 890 96

The epithelial expression of apomucins MUC1, MUC2, MUC3, and MUC5/6 was examined in normal pancreas and in pancreatic lesions, using immunohistochemical methods. In normal pancreas (n = 5), MUC1 apomucin was expressed in ducts and some acini, but there was no expression of MUC2, MUC3, or MUC5/6. In chronic pancreatitis (n = 5), MUC1 apomucin was expressed, but expression of the other apomucins was not noted. However, mucous hyperplastic foci of pancreatic ducts expressed MUC5/6 apomucin in 2/5 cases (40 percent). In intraductal papillary-mucinous neoplasm (IPMN) of the pancreas (n = 9), MUC1, MUC2, MUC3, and MUC5/6 apomucins were expressed in 8/9 (89 percent), 0/9 (0 per cent), 4/9 (44 per cent), and 9/9 (100 per cent) case, respectively. In pancreatic mucinous cystadenoma (n = 8), MUC1, MUC2, MUC3, and MUC5/6 apomucins were expressed in 7/8 (88 percent), 0/8 (0 percent), (25 percent), and 3/8 (38 percent) cases, respectively. In invasive ductal adenocarcinoma of the pancreas (n = 25), expression of MUC1, MUC2, MUC3, and MUC5/6 apomucins was found in 25/25 (100 percent), 1/25 (4 percent), 20/25 (80 percent), and 24/25 (96 percent) cases, respectively. Atypical mucous duct hyperplasia near cancer cells consistently expressed MUC1 apomucin and occasionally expressed MUC3 and MUC5/6. In positive cases, MUC1 apomucin expression was noted in the cell membrane facing the ductal or neoplastic lumina, while expression of MUC2, MUC3, and MUC5/6 apomucins was found in the cytoplasm. These results suggest that MUC3 and MUC5/6 apomucins newly emerge during the neoplastic transformation of pancreatic mucinous cystadenoma and IPMN and during pancreatic ductal carcinogenesis, while MUC1 apomucin remains positive and MUC2 apomucin remains almost negative during neoplastic transformation.
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PMID:Expression of MUC apomucins in normal pancreas and pancreatic tumours. 897 74

In an attempt to seek out new factors that are related to colorectal carcinogenesis at the molecular level, subtractive hybridization between cDNA of normal mucosal tissues and mRNA of colorectal carcinoma tissues was performed. Subsequent screenings of the cDNA libraries, constructed from normal mucosal tissues, using the "subtractive probes" generated a total of 46 clones that were expressed in normal mucosa but were either expressed at a significantly reduced level or not expressed at all in cancer tissues. Partial nucleotide sequences of all of these cDNA clones were determined, and sequence homology analyses were performed with the Genbank database. Of the 46 cDNA samples, 44 contained substantial sequence homologies with 32 immunoglobulin gene fragments, a helix-loop-helix basic phosphoprotein gene, an acidic ribosomal phosphoprotein P2 gene, a BLR1 gene for Burkitt's lymphoma receptor 1 gene, D5S419 DNA segment containing (C-A) repeats, a glucokinase (GCK) gene, a Na+, K+-ATPase alpha-subunit gene, a histocompatibility system HLA-DR heavy-chain gene, a dystrophic gene, a mucin (MUC2) gene, a mu-glutathione S-transferase gene, a Menkes disease protein gene, and a 40-kDa keratin intermediate filament precursor gene. The remaining two cDNA clones (now registered under GenBank accession numbers U17714 and U20428) showed few (less than 60%) sequence homologies with any known sequences in the GenBank database and, therefore, may represent novel genes whose expression was down-regulated in human colorectal carcinomas. The possible clinical significance of these findings and the involvement of these two genes in the carcinogenesis of colorectal as well as other cancers are being investigated.
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PMID:Characterization of colorectal-cancer-related cDNA clones obtained by subtractive hybridization screening. 929 8

To date, nine apomucins have been characterized and their expression in malignant and premalignant lesions is under evaluation. The purpose of this study was to characterize immunohistochemically the expression of MUC2 (colonic/ intestinal type), MUC5AC (gastric surface type), and MUC6 (pyloric gland type) apomucins in 55 patients with gallbladder carcinoma (10 with in situ carcinoma, 45 with invasive carcinoma), 20 patients with gallbladder dysplasia, and 15 patients with non-dysplastic gallbladder. MUC2 was expressed mainly in 'goblet type' cells. The frequency was increased in non-dysplastic gallbladder (47%), dysplasia (75%), and in situ carcinoma (100%), and decreased in invasive carcinoma (58%). Carcinoma cells expressing MUC2, which were usually distributed at superficial areas, and well-differentiated carcinoma expressed MUC2 more extensively than moderately and poorly differentiated ones. MUC5AC was frequently expressed in gallbladder irrespective of non-dysplastic epithelia, dysplasia and carcinoma. MUC5AC was expressed also in carcinoma cells at deeply invasive sites. MUC6 was expressed frequently in pseudopyloric gland metaplasia as well as dysplasia and carcinoma. In conclusion, non-dysplastic gallbladder has a similar phenotype to gastric pyloric mucosa. Gallbladder carcinoma exhibits both intestinal and gastric surface phenotypes in the early stage of carcinogenesis, with the gastric surface phenotype dominant in invasive carcinoma.
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PMID:Expression of MUC2, MUC5AC and MUC6 apomucins in carcinoma, dysplasia and non-dysplastic epithelia of the gallbladder. 1022 23

Although the loss of sulfomucins was known as an indicator of carcinogenesis and malignant progression of colonic epithelia, it was not known whether the loss was directly related to the malignant behavior of colon carcinoma cells. We have studied the biological properties of LS174T human colon carcinoma cells before and after suppression of sulfomucin production. Incorporation of [35S]-sulfate into high molecular weight mucins decreased after carcinoma cell treatment with 1.5% dimethylsulfoxide (DMSO) for 8 days. The amounts of sulfomucin determined using a sulfomucin-specific monoclonal antibody (mAb 91.9H), in Western blot and flowcytometric analyses, also decreased. In addition, the levels of MUC2 and MUC5B mucin gene expression measured by RT-PCR were reduced after DMSO-treatment, whereas the levels of MUC1, MUC5AC, and MUC6 mucin gene expression were not. The DMSO-treated cells were tested in vitro and in vivo for their properties. Differences were not detected in their anchorage-independent growth, anchorage-dependent growth, E-selectin-dependent cell adhesion or sensitivity to interleukin (IL)-2-activated lymphocyte cytolysis. When untreated or DMSO-treated LS174T cells were injected intrasplenically into nude mice, the treated cells lacking certain cell surface sulfomucins formed fewer metastatic colonies in the liver. These results suggest that the loss of sulfomucins by colonic epithelial cells during progression is not directly related to the enhanced malignant behavior.
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PMID:Malignant and other properties of human colon carcinoma cells after suppression of sulfomucin production in vitro. 1041 Nov

The purpose of this study was to determine whether mucin expression is altered in laryngeal cancer. MUC1 and MUC2 mucin expression was examined in biopsy specimens from 80 patients that comprised 23 laryngeal dysplasias, 36 laryngeal carcinomas, and 21 normal larynx control specimens. High MUC1 expression was found in all 3 groups (P = 0.689, Fisher exact test). However, significantly higher levels of MUC2 expression were detected in carcinomas compared with dysplasias and control specimens (P = 0.009, Fisher exact test). Altered MUC2 expression may be an important step in carcinogenesis in laryngeal cancer.
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PMID:Altered MUC1 and MUC2 glycoprotein expression in laryngeal cancer. 1122 57

In normal stomach, MUC5AC and MUC6 apomucins are associated with Lewis types 1 and 2, respectively, and this association is lost during gastric carcinogenesis. The expression of gastric (MUC5AC, MUC6) and intestinal (MUC2, MUC4) apomucins and Lewis antigens during gastric development, using single and double labeling immunohistochemistry on fetal tissues (15-41 weeks), was analyzed and related to the tumor expression patterns. Apomucin expression in other fetal tissues was also analyzed. In gastric samples, MUC2 is detected in 14 of 19 showing no correlation with fetal age, and MUC4 is not detected. MUC5AC and MUC6 are always highly detected and are coexpressed and associated with both types of Lewis antigens. These patterns change progressively with the development of the adult gastric morphology. MUC2 is detected in the small intestine, colon, and pancreas; MUC4 is expressed in the colon; MUC5AC is detected in the small intestine; and MUC6 is found in the duodenum and pancreas. The patterns of apomucin expression and association with Lewis antigens during development are complex, but there is a trend toward the establishment of the adult pattern, with the exception of MUC4, which is not detected. These patterns found in fetal stomach indicate that alterations reported in gastric tumors do not fully recapitulate a developmental phenotype.
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PMID:Apomucin expression and association with Lewis antigens during gastric development. 1127 14


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