Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epithelial mucin-1 (MUC1) is an important target antigen that it is overexpressed in both epithelial and haematological cancers including multiple myeloma (MM) and some lymphomas and leukaemias. MUC1 has adhesive and immunosuppressive properties, which may promote cancer progression. These studies evaluated the effect of IFNs on MUC1 expression, since these agents are widely used in clinical cancer therapy. MUC1 and interferon (IFN) receptor expression were measured by radioligand binding. Changes in MUC1 mRNA levels in response to IFN-gamma were assessed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). IFN-gamma was found to be a more potent inducer of MUC1 expression than IFN-alpha. 125I-IFN binding studies indicated that both IFN receptors were expressed in most of the cell lines. With IFN-gamma treatment, there was upregulation of MUC1 mRNA. IFN-gamma has a more consistent and more potent effect upon MUC1 induction than IFN-alpha. The ability to upregulate MUC1 across a broad range of cancer types by a clinically available cytokine, IFN-gamma, has important implications for enhancing immunotherapeutic approaches targeting MUC1.
...
PMID:Interferon-gamma upregulates MUC1 expression in haematopoietic and epithelial cancer cell lines, an effect associated with MUC1 mRNA induction. 1256 94

Abnormal gastro-oesophageal reflux and bile acids have been linked to the presence of Barrett's oesophageal premalignant lesion associated with an increase in mucin-producing goblet cells and MUC4 mucin gene overexpression. However, the molecular mechanisms underlying the regulation of MUC4 by bile acids are unknown. Since total bile is a complex mixture, we undertook to identify which bile acids are responsible for MUC4 up-regulation by using a wide panel of bile acids and their conjugates. MUC4 apomucin expression was studied by immunohistochemistry both in patient biopsies and OE33 oesophageal cancer cell line. MUC4 mRNA levels and promoter regulation were studied by reverse transcriptase-PCR and transient transfection assays respectively. We show that among the bile acids tested, taurocholic, taurodeoxycholic, taurochenodeoxycholic and glycocholic acids and sodium glycocholate are strong activators of MUC4 expression and that this regulation occurs at the transcriptional level. By using specific pharmacological inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase A and protein kinase C, we demonstrate that bile acid-mediated up-regulation of MUC4 is promoter-specific and mainly involves activation of phosphatidylinositol 3-kinase. This new mechanism of regulation of MUC4 mucin gene points out an important role for bile acids as key molecules in targeting MUC4 overexpression in early stages of oesophageal carcinogenesis.
...
PMID: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. 1458 90

Members of the cadherin superfamily mediate critical interactions in tissue differentiation and organogenesis, including differentiation and maintenance of the intestine. In this study, we report the identification and expression of a novel cadherin in the intestinal epithelium. We identified this cDNA by subtraction hybridization and obtained subsequent clones by screening a human cDNA library. Tissue distribution of the mRNA encoding the cadherin was assessed by RNA blot, reverse transcriptase PCR, and in situ hybridization. Protein expression was analyzed by protein blot and immunohistochemistry. The cDNA encodes an integral membrane protein with four consecutive cadherin binding domains followed by a series of mucin domains, a unique feature of this cadherin. Differences in the mucin domains account for four splice-forms. Multiple potential SH3-binding domains and a single potential PDZ-binding domain follow the transmembrane domain. Analysis revealed expression in the liver, kidney, and intestine. Three splice variants were found in the embryonic intestine as early as embryonic d 13 and in the adult intestine. The mRNA localizes to the mature enterocytes throughout the mouse small intestine and the protein, including several species from 90 to 100 kD, resides on the enterocyte basolateral membrane. We have identified intestinal expression of a novel cell cadherin with features suggesting the potential to transduce signals from neighboring cells to the cytoplasm.
...
PMID:Expression of a novel cadherin in the mouse and human intestine. 1502 44

Intraductal papillary neoplasia of the liver (IPNL) frequently presents gastrointestinal metaplasia with aberrant expression of MUC2 and MUC5AC and oversecretion of mucin into the ductal lumen. In this study, the involvement of CDX2, a homeodomain protein involved in the regulation of intestinal development and differentiation, in the expression of MUC2 was examined in mucinous intrahepatic cholangiocarcinoma (ICC) (n=7) and IPNL with hepatolithiasis (n=19) with comparison to conventional ICC (n=11), and intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas (n=9 and 11, respectively). A total of 33 cases of hepatolithiasis, extrahepatic biliary obstruction and normal livers were used as the control. Immunohistochemically, both MUC2 and MUC5AC were frequently expressed in mucinous ICC and IPNL, while expression of MUC2 was not seen in conventional ICC. The nuclear expression of CDX2 was closely associated with the expression of MUC2 in mucinous ICC and IPNL. This intimate association of MUC2 and CDX2 was confirmed by double immunostaining. The cytoplasmic CDX2 expression was frequent in the mucinous and the conventional ICC and pancreatic carcinoma, irrespective of MUC2 and MUC5AC expression. CDX2 mRNA was detected in neoplastic cells showing cytoplasmic as well as nuclear expression of CDX2 by reverse transcriptase-polymerase chain reaction. One IPMT expressed MUC2 associated with nuclear CDX2 expression, while the other IPMT and conventional pancreatic carcinoma expressed MUC5AC only. Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous ICC and IPNL associated with hepatolithiasia, suggesting its role in intestinal differentiation and its association with carcinogenesis in these tumors.
...
PMID:Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis. 1504 36

We report the functional characterization of a new UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-T) (EC 2.4.1.41) from the human disease-causing parasite, Toxoplasma gondii. This glycosyltransferase is denoted as T. gondii ppGalNAc-T3. These enzymes are responsible for the initial step of mucin-type O-glycosylation: the transfer of GalNAc from the UDP-GalNAc nucleotide sugar donor onto a peptide acceptor. Following an in silico analysis of the publicly available T. gondii DNA database, we used molecular biology approaches to identify and isolate the cDNA encoding this enzyme. The resulting type II membrane protein contains N-terminal cytoplasmic, transmembrane, and C-terminal lumenal domains. Conceptual translation of the cDNA sequence also reveals a stem region and the presence of several important sequence motifs. When the recombinant construct was expressed in stably transfected Drosophila melanogaster S2 cells, the purified protein exhibited glycosyltransferase activity in vitro against glycopeptide, but not "naked" peptide, acceptors. In addition, using reverse transcriptase-PCR, T. gondii ppGalNAc-T3 mRNA was equivalently expressed during the tachyzoite and bradyzoite developmental stages. The identification of T. gondii ppGalNAc-T3 as a functional "follow-up" glycopeptide glycosyltransferase further confirms that this human parasite has its own enzymatic O-glycosylation machinery.
...
PMID:Functional characterization of a novel Toxoplasma gondii glycosyltransferase: UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3. 1515 73

Intestinal epithelial cells (IECs) and dendritic cells (DCs) play a pivotal role in antigen sampling and the maintenance of gut homeostasis. However, the interaction of commensal bacteria with the intestinal surface remains incompletely understood. Here we investigated immune cell responses to commensal and pathogenic bacteria. HT-29 human IECs were incubated with Bifidobacterium infantis 35624, Lactobacillus salivarius UCC118 or Salmonella typhimurium UK1 for varying times, or were pretreated with a probiotic for 2 hr prior to stimulation with S. typhimurium or flagellin. Gene arrays were used to examine inflammatory gene expression. Nuclear factor (NF)-kappaB activation, interleukin (IL)-8 secretion, pathogen adherence to IECs, and mucin-3 (MUC3) and E-cadherin gene expression were assayed by TransAM assay, enzyme-linked immunosorbent assay (ELISA), fluorescence, and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. IL-10 and tumour necrosis factor (TNF)-alpha secretion by bacteria-treated peripheral blood-derived DCs were measured using ELISA. S. typhimurium increased expression of 36 of the 847 immune-related genes assayed, including NF-kappaB and IL-8. The commensal bacteria did not alter expression levels of any of the 847 genes. However, B. infantis and L. salivarius attenuated both IL-8 secretion at baseline and S. typhimurium-induced pro-inflammatory responses. B. infantis also limited flagellin-induced IL-8 protein secretion. The commensal bacteria did not increase MUC3or E-cadherin expression, or interfere with pathogen binding to HT-29 cells, but they did stimulate IL-10 and TNF-alpha secretion by DCs. The data demonstrate that, although the intestinal epithelium is immunologically quiescent when it encounters B. infantis or L. salivarius, these commensal bacteria exert immunomodulatory effects on intestinal immune cells that mediate host responses to flagellin and enteric pathogens.
...
PMID:Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius. 1677 55

Aquaporin 3 (AQP3) acts as the membrane channel of water and other small solutes and plays a major role in fluid homeostasis. To investigate the expression of AQP3 in normal and neoplastic lung tissues, we studied a series of 149 lung carcinoma tissues and 2 cell lines by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction. In normal lung tissues, immunohistochemical expression of AQP3 was demonstrated in bronchial basal cells, alveolar type II cells, bronchiolar epithelial cells, and secretory cells of submucosal glands. In lung carcinomas, AQP3 expression was observed in 59 (70.2%) of 84 adenocarcinomas. Squamous cell carcinoma and large cell carcinoma had rather low positive ratios (35.8% and 13.4%, respectively). No AQP3 expression was demonstrated in small cell carcinoma, pleomorphic carcinoma, or metastatic colon adenocarcinoma. In adenocarcinomas, AQP3 was detected in all tumors of bronchioloalveolar subtype. Papillary subtype also showed a higher positive ratio of AQP3 compared with that in acinar and solid with mucin subtypes. In addition, AQP3 expression was related to tumor differentiation and clinical stage in adenocarcinomas. Western blotting and reverse transcriptase-polymerase chain reaction analyses confirmed the expression of AQP3 protein and messenger RNA in cell lines and tissues of lung adenocarcinoma. We conclude that AQP3 is widely expressed in the normal respiratory tract and can play an important role in the maintenance of water homeostasis. In addition, lung carcinomas, especially adenocarcinomas, can produce AQP3, possibly in connection with their functional and/or biological nature, although the detailed mechanism of AQP3 expression in lung carcinomas remains to be clarified.
...
PMID:Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues. 1705 99

Asthma is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC1) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of Calcium-activated chloride channel 1 (CaCC1) and mucus overproduction in Chinese asthmatic airway, the expression of CaCC1, mucin 5AC (MUC5AC) and mucus in bronchial tissues were examined. Bronchial tissues were isolated from non-cancerous areas of lungs obtained following resection for lung neoplasm in West China Hospital from April to July in 2004. Six patients were diagnosed lung neoplasm with moderate asthma, and other ten were diagnosed lung neoplasm without asthma as the control subjects. The expression of CaCC1, MUC5AC and mucin in bronchial tissues was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridized with digoxigenin (DIG)-labeled RNA probe, immunohistochemical and Alcian blue-periodic acid Schiff (AB-PAS) staining, respectively. In RT-PCR, two expression patterns of CaCC1 mRNA were found, which were located in the 450 bp and 510 bp. With in situ hybridization, a stronger expression of CaCC1 mRNA was further detected throughout the bronchial tissues from patients with asthma than control subjects (P<0.01); Samples from asthmatics were showed a stronger staining for MUC5AC than those in control subjects (P<0.05); AB-PAS staining revealed more mucins and goblet cells in asthmatic bronchial epithelium and submucosal gland comparing to that in control subjects (P<0.05). The increased expression of CaCC1 in asthmatic airways was well correlated with the expression of MUC5AC protein, the percentage of goblet cells and the area of submucosal gland (P<0.01, P<0.01, P<0.05). These results suggest that the up-regulated gene expression of CaCC1 exists, which is complicated with mucus hyper-secretion in Chinese asthmatic airway.
...
PMID:Increased expression of human calcium-activated chloride channel 1 gene is correlated with mucus overproduction in Chinese asthmatic airway. 1769 77

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase-PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC.
...
PMID:MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer. 1847 1

Goblet cell hyperplasia and mucin hypersecretion are important for the expulsion of the intestinal trematode, Gymnophalloides seoi , from mice. However, regulatory mechanisms underlying these processes remain elusive. To better understand the effects of G. seoi antigen on the host's intestinal epithelial cells, we determined whether G. seoi induces expression of Toll-like receptors (TLRs) and mucin-related (MUC) genes on a human intestinal epithelial cell line (HT29 cells). We treated HT29 cells with G. seoi or other adult helminth antigens and measured mRNAs of TLRs and MUCs. We also performed reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry to determine whether TLR and MUC expression is regulated by interferon (IFN)-gamma, interleukin-4, or monoclonal antibodies (mAbs) against G. seoi 46 kDa antigen. Gymnophalloides seoi antigen significantly induced expression of TLR2 and MUC2 in HT29 cells, and IFN-gamma was found to upregulate TLR2 expression on the surface of the cells. The expression of MUC2 was increased by IFN-gamma, but was decreased significantly via the combination of mAbs-to-human TLRs and G. seoi antigen. These results demonstrated that G. seoi antigen upregulates TLR2 and MUC2 expression on human intestinal epithelial cells. These effects reflect a helminth-induced, IFN-gamma-dependent, and innate mucosal immune mechanism in this human intestinal cell line.
...
PMID:Toll-like receptor 2 and Muc2 expression on human intestinal epithelial cells by Gymnophalloides seoi adult antigen. 1973 27


<< Previous 1 2 3 4 5 6 Next >>

---