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)

Telomerase is a specialized type of reverse transcriptase which catalyzes the synthesis and extension of telomeric DNA (for review, see ref.1). This enzyme is highly active in most cancer cells, but is inactive in most somatic cells. This striking observation led to the suggestion that telomerase might be important for the continued growth or progression of cancer cells. However, little is known about the molecular mechanism of telomerase activation in cancer cells. Human telomerase reverse transcriptase (hTRT) has recently been identified as a putative human telomerase catalytic subunit. We transfected the gene encoding hTRT into telomerase-negative human normal fibroblast cells and demonstrated that expression of wild-type hTRT induces telomerase activity, whereas hTRT mutants containing mutations in regions conserved among other reverse transcriptases did not. Hepatocellular carcinoma (20 samples) and non-cancerous liver tissues (19 samples) were examined for telomerase activity and expression of hTRT, the human telomerase RNA component (hTR; encoded by TERC) and the human telomerase-associated protein (hTLP1; encoded by TEP1). A significant correlation between hTRT expression and telomerase activity was observed. These results indicate that the hTRT protein is the catalytic subunit of human telomerase, and that it plays a key role in the activation of telomerase in cancer cells.
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PMID:Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. 942 3

Telomerase is a unique reverse transcriptase involved in the maintenance of telomeric DNA, which is generally undetectable in normal human somatic cells. However, it has been found in organs of normal adult rodents including the liver. In order to elucidate relevant control mechanisms operating in normal somatic cells, we examined telomerase activity in primary cultured rat hepatocytes. During culture under serum-free conditions, rat hepatocytes rapidly lose the ability of organ-specific expression of serum albumin, apolipoprotein A-I, and hepatocyte nuclear factor 4, and the capacity for cytochrome P-450 induction by xenobiotics. The telomerase activity was found to be concomitantly increased about 2. 5-fold at 48 h and 3-fold at 72 h. Northern blot and RT-PCR analyses with primary cultured hepatocytes revealed the associated accumulation of rat telomerase RNA subunits (TR), and the mRNAs for a telomerase reverse transcriptase (TERT) and a telomerase-associated protein (TEP1). The activity of hepatocyte telomerase, which was elevated during the primary culture, increased further when the cells were stimulated with hepatocyte growth factor. In this case, however, the levels of TR, TERT, and TEP1 mRNA did not show any detectable changes.
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PMID:Up-regulation of telomerase in primary cultured rat hepatocytes. 1042 30

The aim of this study is to investigate the effect of the p21 gene transfection on the growth of cultured human glioma cell lines, and analyze the telomerase activity, and detection of telomerase components in p21 transfectant. The p21 gene was transfected into human glioma cell lines, U251MG and T98G with our novel liposome. The cell growth was assessed by counting the number of trypan blue-excluding cells in a hemocytometer and flow cytometry analysis. The expression of P21 protein and its mRNA were examined by Western and Northern blot analysis. The telomerase activity was assayed by TRAP (telomerase repeat amplification protocol)/TRAP-HPA (hybridization protection assay) method qualitatively and quantitatively. The length of telomere was measured by Southern blot analysis. The expression of telomerase components (hTERT, hTERC and TEP1) were examined by RT-PCR (reverse transcriptase-polymerase chain reaction). The p21 transfectant demonstrated the expression of P21 protein and its mRNA. The p21 transfection of human glioma cells results in growth inhibition and G0/G1 arrest. The p21 transfectant revealed a decrease of telomerase activity and hTERT expression as compared with control cells. These results suggest that p21 transfection induces G0/G1 arrest in human glioma cells which associates with the reduction in the telomerase activity and hTERT expression.
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PMID:Growth inhibition of human glioma cells by transfection-induced P21 and its effects on telomerase activity. 1093 98

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

Several types of tumors are known to originate from the pineal region, among them pineal parenchymal tumors (PPTs) and papillary tumors of the pineal region (PTPRs), probably derived from the subcommissural organ. As a result of their rarity, their histologic diagnosis remains difficult. To identify molecular markers, using CodeLink oligonucleotide arrays, gene expression was studied in 3 PPTs (2 pineocytomas and one pineoblastoma), 2 PTPRs, and one chordoid glioma, another rare tumor of the third ventricle. Because PTPR and chordoid glioma may present ependymal differentiation, gene expression was also analyzed in 4 ependymomas. The gene patterns of the 3 PPTs fell in the same cluster. The pineocytomas showed high expression of TPH, HIOMT, and genes related to phototransduction in the retina (OPN4, RGS16, and CRB3), whereas the pineoblastoma showed high expression of UBEC2, SOX4, TERT, TEP1, PRAME, CD24, POU4F2, and HOXD13. Using reverse transcriptase-polymerase chain reaction on 13 PPTs, we demonstrated that PRAME, CD24, POU4F2, and HOXD13 might be candidates for grading PPT with intermediate differentiation. PTPRs, classified with chordoid glioma and separately from ependymomas, showed high expression of SPEDF, KRT18, and genes encoding proteins reported to be expressed in the subcommissural organ, namely ZFH4, RFX3, TTR, and CGRP. Our results highlight the usefulness of gene expression profiling for classify tumors of the pineal region and identify genes with potential use as diagnostic markers.
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PMID:Microarray analysis reveals differential gene expression patterns in tumors of the pineal region. 1682 54