Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of experiments were conducted to study synthesis and secretion of mucin in mucus-secreting subpopulations of HT29 human colonic adenocarcinoma cells selected by resistance to methotrexate (MTX). Mucin was quantitated by [3H]glucosamine labeling and chromatography on Sepharose CL-4B. The mucinous nature of the labeled high molecular weight glycoprotein was verified by alkaline borohydride treatment, cesium chloride density gradient ultracentrifugation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these experiments demonstrated that MTX-treated cells have increased amounts of mucin in medium, cytosol, and membrane fractions. This was associated with the increase in the activities of polypeptidyl-N-acetylgalactosaminyltransferase and beta-1,3-galactosyltransferase compared to control cells. DEAE-Sephacel chromatography of [3H]glucosamine-labeled high molecular weight glycoproteins suggest that MTX-treated cells are less acidic compared to controls. Using complementary DNA probes for two distinct human intestinal mucins (MUC2 and MUC3) and one mammary mucin (MUC1), it was found that MTX-treated cells expressed more mucin messages compared to untreated cells. These results were consistent with immunoblots using anti-MRP (MUC2 repeat peptide), anti-M3P (MUC3 repeat peptide), 139H2 (MUC1 peptide), anti-T (peanut lectin), anti-Tn (91S8), and anti-sialosyl Tn (JT10e) antibodies. These data indicate that MTX-resistant HT29 cells show enhanced secretion and synthesis of mucin as well as expression of MUC1-, MUC2-, and MUC3-related mucin polypeptide epitopes.
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PMID:Expression and characterization of mucins associated with the resistance to methotrexate of human colonic adenocarcinoma cell line HT29. 151 31

A mucus secreting, clonal derivative (HT29-SB) of the human colonic adenocarcinoma cell line HT29, and the LS174T colon cancer cell line, secrete mucin into the culture medium as a viscoelastic gel. Mab BC2, which defines a peptide epitope present in the variable number of tandem repeats (VNTR) of the MUC1 core protein, reacted with this material after deglycosylation. Two high molecular weight bands were detected in TFMSA treated gel-formed mucin from HT29-SB and LS174T by western blotting (Mr 580 kDa and 420 kDa). A similar pattern of reactivity was seen with the culture supernatants from HT29-SB, the ovarian tumor cell line COLO-316, and the breast cancer cell line MCF-7. Mab CCP58 (anti-MUC2 VNTR) reacted with a 580 kDa band in gel-formed mucin produced by LS174T, but was not reactive with mucin produced by the other cell lines. The findings indicate that human colonic cell lines, in addition to breast and ovarian cell lines, may both express and secrete the MUC1 protein core, and that the LS174T cell line expresses and secretes both the MUC1 and MUC2 core proteins.
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PMID:Production of MUC1 and MUC2 mucins by human tumor cell lines. 171 49

Expression of sulfated carbohydrate chains in intestinal metaplasia (IM) and gastric cancer tissues was immunohistochemically evaluated by using a monoclonal antibody (MAb) 91.9H. While normal gastric tissues were negative for MAb 91.9H, IM and cancer tissues were positively stained with high frequency. The incidence was 67% for IM with chronic gastritis (n = 12), 95% for IM with gastric cancer (n = 21), 77% for well and moderately differentiated adenocarcinoma (n = 13), 48% for poorly differentiated adenocarcinoma (n = 23), 89% for signet-ring cell carcinoma (n = 9) and 100% for mucinous adenocarcinoma (n = 7). When poorly differentiated adenocarcinoma cases were divided into two groups, solid (n = 13) and non-solid types (n = 10), the incidences were 8% and 100%, respectively. These data suggest that MAb 91.9H could be of practical use as a new marker for IM and gastric cancer, and may be valuable for subgrouping poorly differentiated adenocarcinomas. Analyses of the core proteins for 91.9H epitope were then carried out. Comparison of immunostaining of ten poorly differentiated adenocarcinoma cases by MAb MUSE11 against MUC1 gene product with that by MAb 91.9H suggested that 91.9H epitope is not expressed on MUC1. Northern blot analysis of 10 pairs of gastric cancer and adjacent normal tissues with a MUC2 cDNA probe showed that the expression level of MUC2 mRNA was below the limit of detection. Thus, 91.9H epitope may be expressed on other proteins than MUC1 or MUC2 core proteins in gastric cancer.
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PMID:Expression of sulfated carbohydrate chains detected by monoclonal antibody 91.9H in human gastric cancer tissues. 751 85

Mucin glycoproteins (mucins) are the major macromolecular constituents of mucus gels in mammalian respiratory, gastrointestinal, and reproductive tracts. Disorders of mucin glycosylation, which may result from either abnormal post-translational processing or differences in mucin protein gene expression, have been indicated in several diseases. Quantitation of mucin gene expression has been hindered by two features of human mucin genes: variable numbers of tandemly repeating nucleotides per mRNA molecule and polydisperse mRNA transcripts. We report here a method to quantitate mucin mRNA levels in epithelial cells and have evaluated three mucin genes, MUC1, MUC2, and MUC5, which are expressed in respiratory epithelium. The method uses the 3' non-tandem repeat mucin cDNA sequences, as they were shown to have a single-size transcript when amplified by the polymerase chain reaction, consistent with a one-to-one relationship with the mRNA molecule. The 3' non-tandem repeat cDNA sequences were cloned and transcribed in vitro to prepare complementary RNA (cRNA) standards. By comparison to a cRNA standard curve, mucin gene expression was evaluated in colon adenocarcinoma, pancreatic adenocarcinoma, and transformed respiratory epithelial cells and in nasal polyp tissue by slot blot analysis. CFPAC-1, a pancreatic adenocarcinoma cell line, expressed the highest MUC1 transcript levels. Colon adenocarcinoma cell lines varied in MUC2 expression levels, and one colon adenocarcinoma cell line, HT-29, had higher levels of MUC5 than MUC2. Nasal polyp tissue expressed more MUC5 mRNA than MUC1 or MUC2 mRNA. This mucin mRNA slot blot method provides a quantitative method for investigating the regulation of mucin gene expression in health and disease.
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PMID:Quantitation of mucin mRNA in respiratory and intestinal epithelial cells. 794 2

The expression pattern of mucin genes was studied in 7 lung adenocarcinoma cell lines (CL1, CL2, CL3, NCL2, PC9, PC13, PC14) and 12 lung adenocarcinoma tissues. CL1 and PC13 are poorly differentiated cell lines with low mucin glycoprotein production. The other 5 cell lines are well differentiated and produce a higher amount of mucins. Total RNA was extracted from these cell lines. Northern blot analysis was performed by hybridization with specific antisense oligonucleotide probes recognizing mucin-specific tandem repeats of 4 mucin genes (MUC1, MUC2, MUC3, MUC4). RT-PCR was carried out to amplify the 3' and 5' nonrepetitive coding regions of MUC1 and the 5' nonrepetitive coding region of MUC2. All these cell lines expressed MUC1, MUC2, and MUC4 mRNA but in variable mounts. The poorly differentiated cell lines (CL1 and PC13) had a relatively low level of expression of MUC1, MUC2, MUC3 and MUC4. RT-PCR, with primers amplifying the MUC1 nonrepetitive coding region 5' end, 293 bp, and the 3' end, 522 bp, as well as the MUC2 nonrepetitive 5' coding region, 308 bp, revealed the presence of MUC1 and MUC2 mRNA in all the cell lines. Sequence analysis of the PCR products were very homologous, similar to previously published MUC1 and MUC2 cDNA sequences. The expression pattern of mucin genes is consistent with that of mucin glycoproteins as studied using biochemical and immunological methods. Northern blotting and RT-PCR analysis in 12 lung adenocarcinoma tissues with various grades of differentiation (6 poorly differentiated adenocarcinomas and 6 moderately to well-differentiated adenocarcinomas) showed heterogeneous expression of the 4 mucin genes in tissues without clear correlation with the differentiation grade. Therefore the clinical implications of the differential expression of the mucin genes need further investigation.
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PMID:Mucin mRNA expression in lung adenocarcinoma cell lines and tissues. 860 37

Recent molecular biological approach has revealed the primary structure of some mucin core proteins. Most prominent characteristic is tandemly repeated sequences. cDNA cloning of 8 kinds of mucin core proteins, MUC1-7, have thus been performed. Among them, the entire structure was revealed on MUC1,2 and 7. MUC1 is a type I transmembrane protein with a large number of tandem repeat consisting of 20 amino acids. We have found that mouse MoAb MUSE11 against adenocarcinoma, which detects circulating MUC1 in patients with gastrointestinal and pancreatic cancers, recognizes part of the tandem repeat of MUC1 using synthetic peptides. We have transfected MUC1 cDNA to some cell lines, and they indicated that cell-cell and cell-matrix adhesion, growth rate and reactivity with growth factor were suppressed. To date, some of the MoAbs to adenocarcinoma have been shown to react with PDTRP sequence in the tandem repeat of MUC1 (MUC1 epitope), suggesting that MUC1 epitope could be highly immunogenic in human. Recently, cytotoxic T-cells against MUC1 epitope were established from breast and pancreas cancer patients. We also induce those T-cells from the patient with multiple myeloma. Interestingly, CTL functions in an HLA-unrestricted manner, and may be of use an adoptive immunotherapy. MUC2, a large secretory type mucin, cysteine-rich subdomains located both upstream and downstream of its central repetitive region, and these subdomains have sequence similarity with von Willebrand factor. We have shown that anti MUC2 core-protein MoAb CCP58 reacts intestinal metaplasia and cancer in stomach, but not normal gastric mucous membrane. Recently we established a new monoclonal antibody against purified deglycosylated gastric mucin. This antigen was expressed in the deep portion of metaplastic glands and cancers in the stomach. Two cDNA clones coding for this antigenic molecule were obtained.
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PMID:[New mucin core protein genes and their clinical application]. 864 70

This work evaluates the expression in lung cancer of the most well characterized mucin genes (MUC1, MUC2, MUC3) and of the recently described MUC4 in lung tissues, to check a correlation between the expression of any particular gene and this tumor. Hybridization with synthetic oligonucleotides obtained from a part of the sequences of MUC1, MUC2, MUC3 and MUC4, was performed on blotted RNA from 18 lung cancer tissue specimens and from 10 normal tissues samples taken, when possible, from the normal lung counterpart. By means of Northern blot analysis MUC1 revealed to be the most expressed mucin gene in lung cancer, followed by MUC4; by contrast, the expression of MUC2 and MUC3 was almost undetectable in all cancer specimens. The intensity of expression of MUC1 and MUC4 was always superior in cancer tissue than in the normal counterpart. As expected, the highest reactivity for MUC1 and MUC4 expression was observed mainly in the adenocarcinoma histotype which is mucin secreting. These findings represent a contribution to the study of mucin gene pattern in lung cancer, and, in particular, indicate that MUC4, in association with the MUC1 gene, seems to be strongly expressed in this neoplastic disease.
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PMID:Pattern of mucin gene expression in normal and neoplastic lung tissues. 869 45

Mucinous (colloid) carcinoma and well- to moderately-differentiated adenocarcinoma of the colon differ in the pattern and the amount of mucin secretion and perhaps in their behaviour and clinical outcome. To ascertain why these differences exist and to elucidate the mechanisms of tumour progression, we examined two model human cell lines derived from colorectal mucinous carcinoma (C1a) and moderately differentiated adenocarcinoma (HM3) which show typical pathological and mucin staining patterns of the respective type of carcinomas to nude mouse tumour xenografts. Specifically, we sought to determine if there were quantitative and qualitative differences in mucin synthesis, in mucin gene expression and in biological properties between the two model cell lines. Northern blot analysis showed that MUC2 mRNA levels were significantly higher in C1a cells compared with HM3 cells, while those of MUC3, -5 and -6 mRNA were lower. C1a cells secreted approximately five times more radiolabelled apomucin and 1.5 times more glycosylated apomucin than HM3 cells. When the carbohydrate side-chain length of secreted mucins by these cell lines were examined by beta-elimination followed by P4 column chromatography, C1a mucins had mostly short carbohydrate side-chains, while HM3 cells had predominantly longer side-chains. Western blot analysis of the cell homogenate showed higher expression of MUC2 apomucin and mucin-associated carbohydrate antigens, such as T, Tn and sialyl Tn, with decreased sialyl Le(x) expression in C1a cells compared with HM3. Immunohistochemical analysis of 35 colorectal adenocarcinoma and 25 mucinous colorectal carcinoma tissues also demonstrated increased MUC2 apomucin, T, Tn and sialyl Tn antigens in the mucinous cancer specimens. Examination of the biological properties of these cell lines showed that C1a cells had significantly higher in vitro invasive activity in assays of invasion and collagenase activity and significantly lower E-selectin binding and liver colonisation activities in nude mice. These results indicate that colorectal mucinous carcinoma cells differ considerably from colorectal adenocarcinoma cells, both qualitatively and quantitatively, in the pattern of mucin gene expression and in the synthesis and secretion of mucin. In addition, biological studies showed that mucinous carcinoma cells have a greater degree of invasiveness, but less liver colonising activity. These results suggest that the biological and mucin characteristics of mucinous carcinoma cells contribute to extensive local invasion through tissue stroma as the predominant mechanism of tumour progression, while the biological and mucin characteristics of well- to moderately-differentiated colorectal adenocarcinoma contribute to progression via distant metastasis formation.
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PMID:Mucins secreted by cell lines derived from colorectal mucinous carcinoma and adenocarcinoma. 929 18

The striking differences in the histological features of gastric cancers in young and old adults have been thought to be related to differences in the biological behavior of these cancers. Recently, a new grading system (Goseki's classification) showed that the prognosis of the patient is particularly related to the mucin content of the carcinoma. In this study, we examined differences in mucin antigen expression in cancers from young and old adults and whether antigen expression is related to the clinical outcome. The expression of two mucin core proteins (DF3 antigen [MUC1 gene product] and MRP antigen [MUC2 gene product] and a mucin-type carbohydrate antigen [sialosyl-Tn; STn]) was examined immunohistochemically in gastric cancers from 69 young adults (30 to 39 years of age) and 110 old adults (80 to 89 years of age). The incidence rates of the three histological types (tubular adenocarcinoma, poorly differentiated adenocarcinoma, and signet-ring cell carcinoma) were different in the young and old adults. However, among the mucin antigens examined, only DF3 showed significantly higher frequency of expression in the old adults, and the difference was seen only in tubular adenocarcinomas (young, 43%; old, 68%) and poorly differentiated adenocarcinomas (young, 19%; old, 49%). In these two histological types, there was no difference in the frequency of MRP or STn expression between the young and old adults, although the old adults showed a high incidence of intestinal metaplasia that was positive for both antigens. Signet-ring cell carcinomas showed no significant difference in expression rates of the three antigens in young and old adults, but there were significantly higher expression rates in young patients for both MRP (young, 67%; old, 65%) and STn (young, 71%; old, 57%) and a lower rate of DF3 expression (young, 0%; old, 14%). In both young and old adults, the patients with DF3-positive carcinomas showed significantly poorer survival than those without DF3 expression, whereas there was not significant difference in the survival of the patient groups with positive and negative MRP or STn reactivity. In conclusion, the expression of DF3 was influenced by the age of patients and was related to the outcome. In contrast, MRP and STn expression was related more to the histological pattern of the tumor than to the age of the patient and did not correlate with the outcome.
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PMID:Mucin antigen expression in gastric carcinomas of young and old adults. 930 30

De-glycosylation of mucins may expose new tumor-associated core protein epitopes. In this study, to attempt to develop useful markers for gastric cancers, we have purified and de-glycosylated gastric mucin and tried to establish monoclonal antibodies (MAbs). A MAb designated A3D4 among established MAbs was shown to react with gastric cancer with high frequency, but not with normal gastric epithelium. Among normal digestive organs, only the colon and gall bladder were positive for MAb A3D4. The incidence of positivity in gastric cancer was 75% for intestinal-type adenocarcinoma (n = 28), 40% for solid-type adenocarcinoma (n = 5) and 33% for signet/scirrhous-type adenocarcinoma (n = 15). Interestingly, adenoma and intestinal metaplasia (IM) with chronic gastritis or peptic ulcer were negative for MAb A3D4, whereas 8 out of 13 cases (62%) of IM with gastric cancer was positive. Western-blot analysis using the lysate from normal colon tissues revealed a high-molecular-weight (> 300-kDa) smear-like band. Immunohistochemical analysis indicated that the reactivity of MAb A3D4 was clearly increased when tissue sections were pre-treated with periodic acid or O-glycanase, while it was decreased by pre-treatment with trypsin or protease V8. There was no reactivity with the synthetic peptide encompassing the tandem-repeat sequence of MUC2 or MUC3. These data suggest that MAb A3D4 detects a novel gastric-cancer-associated mucin antigen whose epitope may be peptide in nature.
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PMID:A novel gastric-cancer-associated mucin antigen defined by a monoclonal antibody A3D4. 939 54


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