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)

We studied three keratin (K) gene candidates, K13, K19, and K20 mRNAs, for detecting micrometastases in cervical lymph nodes (LNs) by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 166 histologically metastasis-negative nodes, 24 micrometastatic LNs (14. 4%) were detected based on K13 gene expression. Keratin 19 mRNA is an inadequate marker for the genetic diagnosis due to not only illegitimate gene expression from lymphatic tissue but also gene expression from the ectopic salivary gland. Keratin 20 mRNA showed low sensitivity. It is suggested that K13 mRNA may be a promising tumor marker among these keratin genes for detecting the micrometastases in cervical LNs of oral cancer.
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PMID:Keratin mRNA for detecting micrometastasis in cervical lymph nodes of oral cancer. 1109 92

In the process of metastasis, cancer cells secrete several enzymes which degrade extracellular matrices (ECMs) and basement membranes (BMs) of blood vessels. One of them, heparanase, has been reported to be an important enzyme when metastatic cancer cells invade blood vessels. The enzyme cleaves heparan sulfate (HS), a main component of ECM and BM. In the present study, HS-degrading ability of several human oral cancer cell lines (HSC2, HSC3, HSC4, Ca9-22, NA, ACC3 and Ab-J) and tissues derived from human oral squamous cell carcinomas (both metastatic and non-metastatic) were investigated by measuring heparanase activities and levels of heparanase mRNA by a quantitative reverse transcriptase-polymerase chain reaction. The catalytic activities and the mRNA levels of heparanase showed a good agreement. Clinical demonstration of cancer metastasis generally correlated with high levels of heparanase activity and its mRNA. The results suggest that heparanase activity and its mRNA level are good diagnostic parameters for evaluating the metastatic properties of human oral cancer cells.
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PMID:Expression of heparanase in oral cancer cell lines and oral cancer tissues. 1116 46

Telomerase is a specialized reverse transcriptase responsible for synthesizing telomeric DNA at the ends of chromosomes. Six subunits composing the telomerase complex have been cloned: hTR (human telomerase RNA), TEP1 (telomerase-associated protein 1), hTERT (human telomerase reverse transcriptase), hsp90 (heat shock protein 90), p23, and dyskerin. In this study, we investigated the role of each the telomerase subunit on the activity of telomerase. Through down- or upregulation of telomerase, we found that only hTERT expression changed proportionally with the level of telomerase activity. The other components, TEP1, hTR, hsp90, p23, and dyskerin remained at high and unchanged levels throughout modulation. In vivo and in vitro experiments with antisense oligonucleotides against each telomerase component were also performed. Telomerase activity was decreased or abolished by antisense treatment. To correlate clinical sample status, four pairs of normal and malignant tissues from patients with oral cancer were examined. Except for the hTERT subunit, which showed differential expression in normal and cancer tissues, all other components were expressed in both normal and malignant tissues. We conclude that hTERT is a regulatable subunit, whereas the other components are expressed more constantly in cells. Although hTERT has a rate-limiting effect on enzyme activity, the other telomerase subunits (hTR, TEP1, hsp90, p23, dyskerin) participated in full enzyme activity. We hypothesize that once hTERT is expressed, all other telomerase subunits can be assembled to form a highly active holoenzyme.
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PMID:Differential regulation of telomerase activity by six telomerase subunits. 1213 83

Epstein-Barr virus (EBV) persists in the epithelial cells of oral mucosa and often replicates on them. EBV is known to be a causative agent of nasopharyngeal carcinoma. We suspect that EBV may be associated with oral cancers, and thus examined EBV expression on 28 tongues and 9 other oral cancers. We also examined 6 metastatic lesions in the lymph nodes. All cancers were squamous cell carcinoma (SCC). We used mRNA in situ hybridization, immunofluorescence staining, reverse transcriptase-polymerase chain reaction (RT-PCR), and polymerase chain reaction (PCR). The mRNA in situ hybridization using a probe comprising the transcripts of the BamHIW fragment of the EBV genome demonstrated EBV mRNA in the majority of tumor cells in all cases of oral cancer, but in none of the normal tissues. RNA in situ hybridization using an EBER1 probe detected RNAs in 16 out of 24 cancers. Also, mRNA in situ hybridization using a probe of the EBV-determined nuclear antigen-2 (EBNA2) region detected positive signals in 9 out of 12 cancers. Furthermore, EBNA2, latent membrane protein-1 (LMP1) and BZLF1 were detected in these cancers by immunofluorescence staining, but were not detected in any of the epithelial cells of the normal tissues. Four out of 6 metastatic tissues showed stronger fluorescence than that in the primary tissues. RT-PCR analysis also showed EBER1 expression in 1 of the 3 tongue cancers. PCR detected the BamHIW sequence of EBV DNA in all cases, including the normal tissues tested. These findings indicate that EBV may be involved in neoplastic transformation in oral cancers, such as nasopharyngeal carcinoma.
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PMID:Association of Epstein-Barr virus with oral cancers. 1215 59

Chromosomal instability is one of the most important characteristics underlying tumorigenesis. Certain colorectal cancers with chromosomal instability have been shown to have inactivation of a spindle assembly checkpoint party due to mutation of Bub1, a mitotic checkpoint gene. We performed sequencing analysis on reverse transcriptase-polymerase chain reaction (RT-PCR) product of the Bub1 cDNA (entire coding sequence) from 8 human gastric cancer cell lines. In addition, genomic PCR products of Bub1 exon 8, 10, 12, 15 and kinase domain from 9 oral cancer cell lines were analyzed by polymerase chain reaction-single-stand conformation polymorphism (PCR-SSCP). Although sequencing analysis of the Bub1 cDNA revealed several point mutations in 8 gastric cancer cell lines, we could not confirm the mutations by analyzing genomic DNA. Furthermore, genomic PCR-SSCP analysis revealed no mutations in exon 8, 10, 12, 15 and kinase domain of the Bub1 gene in any oral cancer cell lines examined. These results suggest that mutation of the Bub1 gene might not play a role in human stomach and oral carcinogenesis.
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PMID:No mutations of the Bub1 gene in human gastric and oral cancer cell lines. 1237 25

We recently showed that rap1 regulates growth and proliferation in normal keratinocytes, which provoked us to investigate its expression and regulation in malignant cells. Rap1 is variably expressed in whole cell lysates of squamous cell carcinoma (SCC) cell lines. Immunoblot analysis of nuclear and cytosolic fractions and immunohistochemistry revealed that in addition to cytoplasmic expression, SCC cells also exhibit prominent punctate rap1 expression in the nucleus. This unexpected nuclear distribution was confirmed by the evaluation of human oral cancer specimens by immunohistochemistry, which showed both nuclear and cytoplasmic localization. Cytoplasmic rap1 expression was observed mostly in large differentiated cells, whereas nuclear localization was found in morphologically less differentiated cells. Quantitative reverse transcriptase polymerase chain reaction and Northern blot analysis showed that both rap1A and rap1B are expressed in SCC cell lines although rap1B signals are more prominent. Transfection with enhanced GFP-tagged constitutively active and inactive forms of rap1B demonstrated that the active GTP-bound form translocates to the nucleus whereas inactive rap1B(GDP) is retained in the cytoplasm, much of which is in a perinuclear distribution. Furthermore, growth factors induce nuclear translocation of rap1 in oral cancer cells. This novel discovery that active, GTP-bound rap1 translocates to the nucleus makes it only the second of over 100 small GTP-binding proteins to be identified in the nucleus, and the striking prominence of rap1 expression in the nucleus of SCC cells suggests that activated rap1 plays a role in the malignant process.
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PMID:Rap1A and rap1B ras-family proteins are prominently expressed in the nucleus of squamous carcinomas: nuclear translocation of GTP-bound active form. 1367 63

The alpha- and beta- dystroglycan (DG) proteins are involved in epithelial cell development, formation of the basement membrane and maintenance of tissue integrity. Recently, specific changes in the expression patterns of DGs have been described in some cancers. We studied the expression and localisation of alpha- and beta-DG using Western blotting, immunohistochemistry and reverse transcriptase-polymerase chain reaction analyses in samples of normal oral mucosa, oral squamous cell carcinoma (SCC) and cancer cell lines. The alpha- and beta-DG were localised in the basal layers of normal oral mucosa.However, beta-DG expression in cancer tissues showed evidence of aberrant expression, processing and degradation. alpha-DG was altered in all oral cancer samples and cell lines, despite the persistent presence of DG mRNA in cancer cells. Using matrix metalloproteinase (MMP) inhibitors, we determined that beta-DG degradation in carcinoma cell lines can be mediated by MMPs but this process is highly variable, even in cells from the same cancer type. Considering the multifaceted role of DG in epithelial development, it appears that the role of DG degradation in cancer growth and spread, although currently poorly understood, may be important.
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PMID:Aberrant expression, processing and degradation of dystroglycan in squamous cell carcinomas. 1534 90

In the United States, oral cancer accounts for more deaths annually than cervical cancer, leukemias, or Hodgkin's lymphoma. Studies have shown that aberrations of chromosome 18q develop with tumor progression and are associated with significantly decreased survival in head and neck cancer patients. The G-protein-coupled receptor, galanin receptor 1 (GALR1), maps to this region of chromosome 18q. Although the role of GALR1 has been well characterized in neuronal cells, little is known regarding this receptor in non-neuronal cells. In this study, the expression, mitogenic function, and signaling mechanism of GALR1 are investigated in normal and malignant oral epithelial cells. mRNA expression was determined via reverse transcriptase-PCR. Protein quantification was done via immunoblot analysis and enzyme-linked immunosorbent assay. For functional and signaling studies, an inhibitory antibody was generated to the N-terminal ligand binding domain of GALR1. GALR1 protein and mRNA expression and GAL secretion were detected at variable levels in immortalized human oral keratinocytes and human oropharyngeal squamous cell carcinoma cell lines. Upon competitive inhibition of GALR1, proliferation was up-regulated in immortalized and malignant keratinocytes. Furthermore, studies with the inhibitory antibody and U0126, the MAPK inhibitor, show that GALR1 inhibits proliferation in immortalized and malignant keratinocytes by inactivating the MAPK pathway. GALR1s inhibitory effects on proliferation in epithelial cells raises the possibility that inactivation or disregulation of this receptor can lead to uncontrolled proliferation and neoplastic transformation.
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PMID:Galanin receptor 1 has anti-proliferative effects in oral squamous cell carcinoma. 1576 48

This study was designed to identify specific gene expression changes in tongue squamous cell carcinomas (TSCCs) compared with normal tissues using in-house cDNA microarray that comprised of 2304 full-length cDNAs from a cDNA library prepared from normal oral tissues, primary oral cancers, and oral cancer cell lines. The genes identified by our microarray system were further analysed at the mRNA or protein expression level in a series of clinical samples by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis and imuunohositochemistry. The microarray analysis identified a total of 16 genes that were significantly upregulated in common among four TSCC specimens. Consistent with the results of the microarray, increased mRNA levels of selected genes with known molecular functions were found in the four TSCCs. Among genes identified, Rab1a, a member of the Ras oncogene family, was further analysed for its protein expression in 54 TSCCs and 13 premalignant lesions. We found a high prevalence of Rab1A-overexpression not only in TSCCs (98%) but also in premalignant lesions (93%). Thus, our results suggest that rapid characterisation of the target gene(s) for TSCCs can be accomplished using our in-house cDNA microarray analysis combined with the qRT-PCR and immunohistochemistry, and that the Rab1A is a potential biomarker of tongue carcinogenesis.
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PMID:Aberrant expression of RAB1A in human tongue cancer. 1587 Jul 9

Telomerase activity is suppressed in normal human somatic tissues but is activated in cancer cells and immortal cell lines. The reverse transcriptase (RT) subunit human telomerase reverse transcriptase (hTERT) is the key regulator of telomerase activity. The hTERT promoter contains E-box elements and may allow upstream stimulatory factor (USF), a basic helix-loop-helix (bHLH) leucine zipper family proteins, to bind and regulate the expression. In this study, we investigated whether and how USF effect on hTERT. Through luciferase reporter assays, we found that both USF1 and USF2 possess a comparable effect on the inhibition of hTERT expression. Immunoprecipitation (IP) and immunoblotting (IB) analysis reveal that the suppression of hTERT by USF was not through the interaction of USF with c-myc or mad, nor disturbed the cellular protein levels of those. In gel mobility shift and chromatin immunoprecipitation (CHIP) assays, we found that the USF suppression is through direct binding at the E-box site of hTERT promoter and rendering the effect actively. Analysis on clinical normal and tumor tissues reveal that the expression of USF1 and USF2 was lower in the tumor tissues, correlated with hTERT expression and telomerase activity. Taking together, our results demonstrate that USF is a negative transcriptional repressor for hTERT in oral cancer cells. It is possible that USF lose the inhibitory effect on hTERT expression leading to telomerase reactivation and oral carcinogenesis.
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PMID:Upstream stimulatory factor (USF) as a transcriptional suppressor of human telomerase reverse transcriptase (hTERT) in oral cancer cells. 1601 Jun 90


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