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

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

Hypersecretion of mucin is a common feature of chronic and mucoid otitis media which may play an important role in hearing loss. The mechanisms controlling mucin secretion in the middle ear are not completely understood. Our reverse transcriptase-polymerase chain reaction results demonstrate that mRNAs of MUC1, MUC2, MUC3, MUC4 and MUC5AC are expressed in normal rat middle ear mucosa. Moreover, the expression of mRNA of the secretory mucins MUC2, MUC3 and MUC5AC was threefold lower in normal middle ear mucosa than that in the intestine or trachea. In contrast, expression of the membrane-bound mucins MUC1 and MUC4 was approximately the same in both middle ear mucosa and the intestine or trachea. MUC5AC proteins were also identified immunohistochemically in normal rat middle car epithelium. The methodology used in this study provides useful baseline information for investigation of the mechanisms of regulation of mucin gene expression during otitis media.
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PMID:Detection of mucin gene expression in normal rat middle ear mucosa by reverse transcriptase-polymerase chain reaction. 1127 Apr 93

In gastric cancer, altered expression of MUC1, MUC2, MUC5AC, and MUC6 mucin genes has already been described. We show in this report by the means of in situ hybridization, reverse transcriptase-polymerase chain reaction, and transfection assays that MUC5B is also abnormally expressed in gastric carcinomatous tissues and cell lines. We thus undertook to elucidate the molecular mechanisms that regulate the transcription of MUC5B in gastric cancer cells. To this end, high expressing (KATO-III) and low expressing (AGS) gastric cancer cell lines were chosen to study human mucin gene MUC5B expression and promoter activity. Sequencing of the promoter region revealed a distal TATA box located 1 kilobase upstream of the proximal TATA box. Functional activity of the promoter was addressed by using deletion mutants covering 2044 nucleotides upstream of the MUC5B transcription start site. We identified a distal promoter 10 times more active than the proximal promoter in KATO-III cells. In AGS cells, both promoters, much less active, showed the same range of activity. Binding assays allowed us to show that the transcription factor ATF-1 binds to a cis-element present in the distal promoter. Sp1, which binds to both promoters specifically transactivates the proximal promoter. Treatment of transfected cells with PMA, cholera toxin A subunit, and calcium ionophore showed that only PMA led to a substantial activation of the distal promoter. MUC5B 5'-flanking region having a high GC content, influence of methylation on the MUC5B expression was assessed. Our results indicate that repression of MUC5B expression visualized in AGS cells is due in part to the presence of numerous methylated cytosine residues throughout the 5'-flanking region. Altogether these results demonstrate that MUC5B expression in gastric cancer cells is governed by a highly active distal promoter that is up-regulated by protein kinase C and that repression is under the influence of methylation.
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PMID:Aberrant expression of human mucin gene MUC5B in gastric carcinoma and cancer cells. Identification and regulation of a distal promoter. 1127 96

We investigated the expression levels of MUC5AC in endotoxin-induced otitis media with effusion (OME) in the rat using competitive polymerase chain reaction (PCR) and the morphology of middle ear mucosa using transmission electron microscopy (TEM). Experimental OME in the rat was induced after middle ear instillation of Escherichia coli lipopolysaccharides (LPS). Middle ear mucosa were obtained at 0 h, 12 h, Day 1, Day 3, Day 7 and Day 14 and reverse transcriptase (RT)-PCRs were then performed for the identification of MUC1, MUC2, MUC5AC and submandibular mucin 1 expression, followed by competitive PCRs for MUC5AC and beta2-microglobulin expression. Normal middle ear mucosa revealed no expression of mucin genes, whereas endotoxin upregulated the expression of MUC5AC mRNA between 12 h and Day 7, with maximal expression at Days 1 and 3. Middle ears treated three times with LPS upregulated more MUC5AC mRNA expression, by a factor of approximately 3.5, than those 1 day after one instillation. On TEM, dark granulated cells were observed at Day 3 after endotoxin instillation, but mixed granulated cells were seen on the ears treated three times with LPS. These results suggest that MUC5AC could be one of the major mucin genes in the middle ear mucosa related to otitis media.
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PMID:Up-regulation of MUC5AC mRNA expression in endotoxin-induced otitis media. 1142 2

Our purpose was to determine whether peripheral blood biomarkers MUC1 and CK19 could be used to complement imaging studies in differentiating benign from malignant indeterminate pulmonary nodules or masses detected on computed tomography CT. One hundred and eighteen patients had a thoracic CT and blood drawn for tumor marker reverse transcriptase-polymerase chain reaction analysis. Thirty-five of the 118 patients had an indeterminate pulmonary nodular opacity on CT, and the findings then were correlated with the reverse transcriptase-polymerase chain reaction results. The sensitivity and specificity for the markers in determining malignancy was calculated. Thirteen of the 35 opacities on CT proved to be benign, and 22 proved to be lung cancer. Among the patients with indeterminate pulmonary abnormalities, polymorphic epithelial mucin protein 1 had a sensitivity and specificity for lung cancer of 100% and 46%, respectively. Cytokeratin 19 had a sensitivity and specificity for lung cancer of 95% and 8%, respectively. These preliminary data showed that serum biomarkers polymorphic epithelial mucin protein 1 and cytokeratin 19 were not specific for lung cancer, although patients with an indeterminate pulmonary abnormality and negative markers were unlikely to have lung cancer. Integration of imaging studies with the appropriate biomarkers may prove useful in evaluating indeterminate pulmonary nodules or masses.
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PMID:Integration of peripheral blood biomarkers with computed tomography to differentiate benign from malignant pulmonary opacities. 1153 Oct 10

Aberrant expression of mucin genes occurs frequently in advanced cancer. Using quantitative competitive reverse transcriptase/polymerase chain reaction (QC RT-PCR), the expression of three mucin genes--MUC1 (widely expressed in epithelial cells), MUC2 (mainly expressed in intestinal epithelial cells), and MUC5AC (mainly from airway and gastric epithelial cells)--was evaluated in 112 patients with pleural effusions (including 54 cytologically positive malignant pleural effusions, 35 benign exudative pleural fluids, and 23 cytologically negative pleural effusions from cancer patients). The expression ratios of MUC1 and MUC5AC, but not MUC2 gene, were significantly higher in malignant than benign pleural fluids (p < 0.000). The cutoff value, sensitivity, and specificity of MUC1 expression ratio were: 0.126, 64.6%, and 95.7%; and were 0.028, 72.3%, and 95.7%, respectively, for MUC5AC. In combined evaluation with both MUC1 and MUC5AC, the sensitivity was 86.1% and specificity was 91.5%. The positive and negative predictive values were 93.3%, and 82.7%, respectively. We considered mucin QC RT-PCR to be a useful tool in assisting the diagnosis of malignant pleural effusion.
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PMID:Application of mucin quantitative competitive reverse transcription polymerase chain reaction in assisting the diagnosis of malignant pleural effusion. 1167 27

Many theories mention hypersensitive, promiscuous, outlaw or bypass signalling pathways to explain the acquisition of hormone independence in prostate cancer. Hormonal escape of prostate tumours is marked by many biological changes, including mucinous and neuroendocrine differentiation. Since expression of several mucins has been linked to carcinoma tumour progression, we have characterised the expression of mucins at both RNA and protein levels in an in vivo model of prostate cancer in hormonal escape. Using PAC120, a xenograft of a human hormone-dependent prostate tumour, and its hormone-independent variants, we analysed the expression of mucins (MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC6) by immunohistochemistry or reverse transcriptase (RT)-PCR. While the parental PAC120 tumour was a compact poorly-differentiated tumour of Gleason score 9 (5+4), hormone-independent variants displayed mucinous, neuroendocrine-like or mixed histological changes; these changes were stable through serial transplantations or after testosterone supply. MUC1 mRNA was expressed in both PAC120 and the hormone-independent variants, although at variable levels. All tumours displayed a high and constant expression of MUC2 and no expression of MUC4 mRNA. While MUC1 was expressed in all xenografts whatever their hormone dependence status, MUC2, MUC5B and MUC6 were preferentially expressed in hormone-independent variants. The loss of hormone dependence in this prostate cancer xenograft model is therefore marked by irreversible histological alterations, mucinous or neuro-endocrine, associated with an expression of secretory MUC2, MUC5B and MUC6, independent of the histological differentiation subtype. These data point to mucinous differentiation as an important step in the acquisition of hormone independence in this cancer, and suggest that secretory mucins might participate in an unknown pathway of hormonal escape in prostate cancer.
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PMID:Mucinous differentiation features associated with hormonal escape in a human prostate cancer xenograft. 1476 Mar 90

Distant metastasis of colorectal cancer (CRC) occurs mainly in the liver and is the major cause of death. This study explored the overexpression of liver metastasis-associated mRNAs in human CRC by using a well-established, weighted enzymatic chip array platform. Analysis of 10 CRC tissue specimens compared with their normal adjacent tissues revealed that ATP2A2, ELAVL4, hTERT, KCTD2, MUC1, OLFM4, S100B, and TM4SF4 genes were upregulated (gene expression ratio of cancer tissue to paired normal tissue was >2) by microarray and bioinformatics analysis. A gene chip including eight candidate genes was constructed to investigate the circulating tumor cells in blood specimens of 103 preoperative CRC patients and further validated by reverse transcriptase-polymerase chain reaction. Liver metastasis was significantly correlated with overexpression of S100B (p=0.001, OR=9.217), TM4SF3 (p=0.011, OR=4.385), and OLFM4 (p=0.015, OR=3.438). These results suggest that S100B, TM4SF3, and OLFM4 overexpression may affect metastatic behavior of tumor cells in Taiwanese CRC patients.
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PMID:Overexpression of S100B, TM4SF4, and OLFM4 genes is correlated with liver metastasis in Taiwanese colorectal cancer patients. 2201 Oct 44

Impact of different cancer-associated fibroblast (CAF) cell lines on proliferation, migration, invasion and differential expressions of genes in different hepatocellular carcinoma (HCC) cell lines was investigated. Two human CAF cell lines (F26/KMUH, F28/KMUH) and two human HCC cell lines (HCC24/KMUH, HCC38/KMUH) were studied. Influence of F28/KMUH cells on expressions of genes in HCC38/KMUH cells was detected by microarray to select genes for further analysis. Both CAF cell lines promoted proliferation (all P<0.05), migration (all P<0.05) and Matrigel invasion (all P<0.0001) of both HCC cell lines. F26/KMUH cells showed stronger promoted effects on, firstly, proliferation of HCC24/KMUH cells (P=0.0064) and, secondly, migration of both HCC cell lines than F28/KMUH cells did (all P<0.002). Ten up-regulated genes (APLN, CCL2, CCL26, CXCR4, IL6, MUC1, LOXL2, PDGFA, PGK1, VEGFA) related to proliferation, migration, invasion and angiogenesis of HCC detected by microarray were selected for quantitative reverse transcriptase-polymerase chain reaction analysis. Both CAF cell lines had same tendency of effects on differential expressions of genes in same HCC cell line, but expressions of genes between different HCC cell lines were not consistent. Only CCL2, CCL26, IL6 and LOXL2 genes were consistently up-regulated in both HCC cell lines. In conclusion, the effects of CAFs to promote proliferation, migration and invasion of HCC cells are influenced by the characteristics of both CAFs and HCC cells. Up-regulations of CCL2, CCL26, IL6 and LOXL2 genes in cancer cells are part of the common effects of CAFs on HCC cells.
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PMID:Cancer-associated fibroblasts up-regulate CCL2, CCL26, IL6 and LOXL2 genes related to promotion of cancer progression in hepatocellular carcinoma cells. 2273 41

Drug resistance is a major obstacle to the efficient therapy of drug-resistant cancer. To overcome this problem, we constructed a multifunctional DNA origami-based nanocarrier for codelivery of a chemotherapeutic drug (doxorubicin, Dox) and two different antisense oligonucleotides (ASOs; B-cell lymphoma 2 (Bcl2) and P-glycoprotein (P-gp)) into drug-resistant cancer cells for enhanced therapy. To increase the targeting ability of origami, staple strands with 5'-end extended MUC1 sequences were used in the preparation of aptamer-functionalized origami carrying ASOs (Apt-origami-ASO). Dox-loaded Apt-origami-ASO (Apt-Dox-origami-ASO) was prepared by electrostatic adsorption of Dox in origami. Atomic force microscopy (AFM) images demonstrated the successful preparation of Apt-origami-ASO. In vitro studies showed that the Apt-Dox-origami-ASO (Apt-DOA) could controllably release Dox in pH 5.0 phosphate-buffered saline (PBS) buffer and release ASOs in response to glutathione. Further experiments revealed that the origami could protect ASOs against nuclease degradation in 10% FBS. Confocal imaging showed that the Apt-DOA nanocarrier could efficiently enter the Hela/adriamycin (ADR) cells and escape from lysosomes for codelivery of Dox and ASOs into the cytoplasm. The quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot assays testified the efficient silencing of Bcl2 and P-gp mRNA and downregulation of the corresponding protein expressions by Apt-DOA in Hela/ADR cells. Moreover, with the synergetic effect by codelivery of multi-ASOs and Dox, the anticancer assay showed that Apt-DOA could circumvent multidrug resistance and significantly enhance cancer therapy in Hela/ADR and MCF-7/ADR cells. Hence, this multifunctional origami-based codelivery nanocarrier presents a new strategy for efficient therapy of drug-resistant cancer.
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PMID:Aptamer-Functionalized DNA Origami for Targeted Codelivery of Antisense Oligonucleotides and Doxorubicin to Enhance Therapy in Drug-Resistant Cancer Cells. 3181 20

Adrenocortical carcinomas (ACC) are aggressive tumors with a heterogeneous prognosis and limited therapeutic options for advanced stages. This study aims to identify novel drug targets for a personalized treatment in ACC. RNA was isolated from 40 formalin-fixed paraffin-embedded ACC samples. We evaluated gene expression of 84 known cancer drug targets by reverse transcriptase quantitative real time-PCR and calculated fold change using 5 normal adrenal glands as reference (overexpression by fold change >2.0). The most promising candidate cyclin-dependent kinase 4 (CDK4) was investigated at protein level in 104 ACC samples and tested by in vitro experiments in two ACC cell lines (NCI-H295R and MUC1). The most frequently overexpressed genes were TOP2A (100% of cases, median fold change = 16.5), IGF2 (95%, fold change = 52.9), CDK1 (80%, fold change = 6.7), CDK4 (62%, fold change = 2.6), PLK4 (60%, fold change = 2.8), and PLK1 (52%, fold change = 2.3). CDK4 was chosen for functional validation, as it is actionable by approved CDK4/6-inhibitors (e.g., palbociclib). Nuclear immunostaining of CDK4 significantly correlated with mRNA expression (R = 0.52, P < 0.005). We exposed both NCI-H295R and MUC1 cell lines to palbociclib and found a concentration- and time-dependent reduction of cell viability, which was more pronounced in the NCI-H295R cells in line with higher CDK4 expression. Furthermore, we tested palbociclib in combination with insulin-like growth factor 1/insulin receptor inhibitor linsitinib showing an additive effect. In conclusion, we demonstrate that RNA profiling is useful to discover potential drug targets and that CDK4/6 inhibitors are promising candidates for treatment of selected patients with ACC.
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PMID:Targeted Gene Expression Profile Reveals CDK4 as Therapeutic Target for Selected Patients With Adrenocortical Carcinoma. 3237 71


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