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

Some peculiarities of the transcription of human genes with variable number of absolute tandem repeats in the coding region are discussed. The data on the association between short alleles of the apo(a) gene and atherosclerosis are analyzed. Data are described concerning the possible role of the MUC1 gene product, episialin, in carcinogenesis. The possible causes of the polydispersity of apo(a) and mucin gene transcripts are analyzed. It is supposed that RNA polydispersity is the result of the transcription of the repeat. The possible association between repeat transcription and recombination is discussed. The same inverse relationship is noted between the allele length (number of repeats) and the transcription level of the full gene for apo(a) and MUC1 genes. The possible role of the length of VNTR genes as risk factors of human pathogenesis is discussed.
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PMID:[Human genes, containing varying numbers of absolute tandem repeats in the coding area: the possible role in pathogenesis]. 818 60

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

Abnormalities in mucin-type glycoprotein expression have been documented in a variety of cancers, identifying these molecules as targets for immunologically based therapies and prognostic/diagnostic assays. We examined the expression of the membrane-bound MUC1 mucin in normal, histologically atypical, and neoplastic lung to determine its potential contribution to lung carcinogenesis. In vivo, intense MUC1 immunoreactivity was present in normal type II pneumocytes as well as in a range of atypical lesions derived from type II cells and >60% of primary and metastatic non-small cell lung cancers. Expression was not associated with altered survival, although it was highly correlated with the adenocarcinoma histology. A carcinogenesis model using 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone-exposed hamsters revealed that MUC1 mRNA increased prior to the histological appearance of tumors. In vitro studies using MUC1 expressing non-small cell lung cancer cell lines revealed that differentiation away from a type II cell lineage was associated with dramatic down-regulation of MUC1. We propose that MUC1 is a powerful new marker for the type II pneumocyte cell lineage that allows us to follow the type II pneumocyte lineage during the process of lung carcinogenesis.
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PMID:MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis. 985 98

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

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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PMID:Structural organization and classification of the human mucin genes. 1157 69

An important role for beta-catenin pathways in colorectal carcinogenesis was first suggested by the protein's association with adenomatous polyposis coli (APC) protein, and by evidence of dysregulation of beta-catenin protein expression at all stages of the adenoma-carcinoma sequence. Recent studies have, however, shown that yet more components of colorectal carcinogenesis are linked to beta-catenin pathways. Pro-oncogenic factors that also release beta-catenin from the adherens complex and/or encourage translocation to the nucleus include ras, epidermal growth factor (EGF), c-erbB-2, PKC-betaII, MUC1, and PPAR-gamma, whereas anti-oncogenic factors that also inhibit nuclear beta-catenin signaling include transforming growth factor (TGF)-beta, retinoic acid, and vitamin D. Association of nuclear beta-catenin with the T cell factor (TCF)/lymphoid enhancer factor (LEF) family of transcription factors promotes the expression of several compounds that have important roles in the development and progression of colorectal carcinoma, namely: c-myc, cyclin D1, gastrin, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-7, urokinase-type plasminogen activator receptor (aPAR), CD44 proteins, and P-glycoprotein. Finally, genetic aberrations of several components of the beta-catenin pathways, eg, Frizzled (Frz), AXIN, and TCF-4, may potentially contribute to colorectal carcinogenesis. In discussing the above interactions, this review demonstrates that beta-catenin represents a key molecule in the development of colorectal carcinoma.
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PMID:Beta-catenin--a linchpin in colorectal carcinogenesis? 1183 57

The alteration of the mucin profile have been known to play a role in colorectal carcinogenesis. MUC1 is up-regulated and MUC2 is down-regulated in colorectalcarcinomas. Overexpression of p53 is frequently noted in colorectal carcinomas with deep invasion or lymph node metastasis. However, there have been few reports about the association between MUC1, MUC2, and p53 expression with respect to the metastatic potential. This study was aimed to investigate the relationship of MUC1, MUC2, and protein p53 expressions with clinicopathological factors in colorectal carcinomas. Expressions of MUC1, MUC2, and p53 protein were examined immunohistochemically. Of total 97 cancers, 44 (45%) were MUC1 positive, 39 (40%) were MUC2 positive and 58 (59%) showed a p53 overexpression. Coexpression of MUC1 with p53 and dual expression of MUC1 with MUC2 were associated with a higher frequency of lymph node metastasis (p<0.05). The right colon showed a higher MUC1 positivity and frequent lymph node metastasis than the left colon (p<0.05). These results suggest that the coexpression of MUC 1 with p53 or MUC2 are involved in regional lymph node metastasis in colorectal carcinomas. The high expression of MUC1 in the right colon cancer was revealed to relate with lymph node metastasis.
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PMID:Coexpression of MUC1 with p53 or MUC2 correlates with lymph node metastasis in colorectal carcinomas. 1185 May 85


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