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)

Childhood neuroblastoma tumours of the sympathetic nervous system show a remarkable clinical heterogeneity ranging from spontaneous regression to unfavourable outcome despite intensive therapy. Favourable neuroblastomas often express high levels of trkA mRNA, encoding the tyrosine kinase receptor for nerve growth factor. We have investigated mRNA expression for the neurotrophin receptor trkC in 23 primary neuroblastomas using a sensitive RNAase protection assay. TrkC expression was detected in 19 of these tumours at highly variable levels with a 300-fold difference between the highest and lowest values. Significantly higher levels of trkC mRNA were found in tumours from patients with favourable features such as low age (P < 0.012), favourable tumour stage (P < 0.012) and favourable prognosis (P < 0.05). Children with intermediate or high trkC mRNA expression had better prognosis compared with those with low or undetectable levels (83.3% vs 20%, P = 0.005). Further characterisation of trkC mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) showed that mRNA encoding the full-length cytoplasmic tyrosine kinase domain of the receptor was only expressed in a subset of favourable tumours. These data show that favourable neuroblastomas may express the full trkC receptor while advanced tumours, in particular MYCN-amplified neuroblastoma, seem to either express no trkC or truncated trkC receptors of as yet unknown biological function. These data are suggestive of a role for trkC and its preferred ligand neutotrophin-3, NT-3, in neuroblastoma differentiation and/or regression.
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PMID:Expression of mRNA for the neurotrophin receptor trkC in neuroblastomas with favourable tumour stage and good prognosis. 879 81

Human neuroblastoma (NB) cell lines have at least three morphological appearance of neuroblastic (N-type), substrate-adhessive (S-type) and intermediate(I) cells. Our previous study revealed S-type cells expressed alpha-smooth muscle actin, desmin and/or basic-calponin, indicating the plausible smooth muscle cell characteristics of S-type cells. In this study, a new human NB cell line, MP-N-MS, was established from bone marrow metastasis of a one year and six-month old girl with advanced NB, originating from right adrenal gland. Morphology of this cell line is composed of S-type cells. MP-N-MS was identified as a NB cell line by surface membrane antigen analysis and MYCN gene amplification. EWS-FLI1 and EWS-ERG chimeric products, observed in Ewing family tumors, were not detected by RT-PCR (reverse transcriptase-polymerase chain reaction). In cytoskeletal protein analysis, alpha-smooth muscle actin and basic calponin of smooth muscle cell markers were detected. Furthermore, smooth myosin of SM1 isoform was identified in MP-N-MS cell line by immunofluorescence, Western blot and RT-PCR, whereas smooth myosin of SM2 was detected by RT-PCR. MP-N-MS is the first cell line, showing SM1 and SM2 isoforms. The presence of smooth muscle myosin of SM1 and SM2 isoforms in MP-N-MS demonstrated the mature smooth muscle phenotype of this NB cell line, and the ability of NB cells to differentiate into smooth muscle cell.
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PMID:[Smooth muscle myosin of SM1 and SM2 isoforms expressing human neuroblastoma cell line of MP-N-MS]. 1045 5

Alveolar rhabdomyosarcoma (ARMS) is associated with the specific chromosomal translocation (2;13)(q35;q14) or its rarer variant t(1;13)(p36;q14), which produces the fusion gene PAX7-FKHR. Here we describe the human cell line RC2, derived from an ARMS, which harbors a cryptic t(1;13)(p36;q14) and concomitantly shows amplification of the PAX7-FKHR fusion gene and of the MYCN oncogene. The t(1;13) and MYCN oncogene were studied by standard cytogenetic analysis and molecular techniques. The reverse transcriptase polymerase chain reaction demonstrated the expression of PAX7-FKHR mRNA in RC2 cells, although karyotype analysis failed to demonstrate a t(1;13)(p36;q14) chromosomal translocation or a derivative 13 chromosome. Double minute chromosomes were detected in all the metaphases studied. Fluorescence in situ hybridization analysis revealed multiple copies of the PAX7-FKHR fusion gene localized exclusively on a subset of double minutes, whereas multiple copies of MYCN were identified on other double minute chromosomes. Southern-blot analysis demonstrated that RC2 cells contain approximately 20 copies of the MYCN oncogene. So far no continuous RMS cell line carrying the t(1;13)(p36;q14) has been described, and PAX7-FKHR and MYCN amplifications have always been reported to occur separately in rhabdomyosarcoma (RMS). The availability of an ARMS cell line that harbors the t(1;13)(p36;q14) constitutes a useful tool for further understanding the role of the PAX7-FKHR fusion gene in RMS oncogenesis and may improve knowledge of the possible relation between PAX7-FKHR and MYCN amplification.
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PMID:Concomitant amplification and expression of PAX7-FKHR and MYCN in a human rhabdomyosarcoma cell line carrying a cryptic t(1;13)(p36;q14). 1106 97

It has been proposed that the regulation of telomerase takes place at the transcriptional level, the expression of the catalytic subunit human telomerase reverse transcriptase (hTERT) being crucial for telomerase activity (TA). Recently, differential splicing of hTERT mRNA has been demonstrated in various tissues during embryonal development, and it has been suggested that only full-length transcripts translate into functionally active telomerase. With this in view, we analyzed the different hTERT transcripts by reverse transcriptase-polymerase chain reaction in neuroblastic tumors and compared the results with the TA, the tumor growth fraction, and the MYCN status. In a series of 38 neuroblastic tumors, high TA and full-length hTERT transcripts were found in nine samples, whereas nine samples showed absence of both enzymatic activity and hTERT transcripts. Interestingly, in another eight samples, low or absent TA coincided with a lack of full-length hTERT transcripts. Eleven samples contained hTERT transcripts with low or undetectable TA and one sample had low TA but no hTERT transcripts. TA correlated with MYCN amplification and was weakly associated with the proliferative activity. Moreover, a significant correlation with tumor progression was observed. Our findings point at a posttranscriptional regulation of TA in a subset of neuroblastic tumors. Because high TA was detected only in tumors with full-length hTERT transcripts, reverse transcriptase-polymerase chain reaction analysis of archival neuroblastic tumor samples might help to appraise the malignant potential in individual cases.
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PMID:Regulation of telomerase activity by alternate splicing of human telomerase reverse transcriptase mRNA in a subset of neuroblastomas. 1169 53

The serial analysis of gene expression (SAGE) technique was used to generate a database of the most abundant transcripts of the MYCN-amplified neuroblastoma cell line IMR-5. A total of 8568 tags were sequenced and shown to represent 4034 unique tags, each of which corresponds to an individual transcript. Expression levels of genes are reflected by the frequency of occurrence of the respective tags. To validate fidelity of SAGE data, relative abundances of seven transcripts were evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Transcripts that were detected nine times or more (>0.1% of the total tag population) accounted for 36% of the total messenger RNA mass but only 3% of the total number of individual transcripts. A strong preponderance of genes involved in protein synthesis, in particular those encoding for ribosomal proteins, were observed among these high-abundance transcripts. Tags corresponding to the amplified gene DDX1 were conspicuously overrepresented in comparison to the other amplified genes MYCN, neuroblastoma amplified gene and MEIS1, which suggests an additional mechanism apart from genomic amplification contributing to the strong upregulation of this gene. This study provides a comprehensive gene expression profile of neuroblastoma cell line IMR-5 and may be used as a reference database for identification of candidate genes that are involved in etiology and pathogenesis of neuroblastoma.
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PMID:Characterization of the gene expression profile of neuroblastoma cell line IMR-5 using serial analysis of gene expression. 1253 80

Telomerase activity (TA) is the most recently recognized prognostic factor in neuroblastoma, and its outstanding predictive power was documented by several studies. However, TA measurements require fresh tumor tissue that is not always available in daily clinical practice. We previously described a reverse transcriptase-polymerase chain reaction assay that we used to investigate the possible prognostic relevance of the telomerase catalytic subunit, hTERT, at the mRNA level. Because hTERT mRNA undergoes alternative splicing as a regulatory mechanism of TA, we discriminated between truncated and full-length hTERT transcripts. In a retrospective study on 124 neuroblastomas, 56 (45.2%) tumors showed spliced hTERT transcripts, whereas 30 (24.2%) contained full-length hTERT transcripts. The presence of both spliced and full-length hTERT transcripts was significantly associated with MYCN amplification. hTERT in general showed no correlation to other prognostic factors, ie, International Neuroblastoma Staging System stage, International Neuroblastoma Pathology classification grade, or age at diagnosis, whereas the presence of full-length transcripts was significantly associated with higher stages. The presence of any hTERT transcripts carried no significant prognostic information, yet full-length hTERT transcripts were highly predictive of poor outcome (P < 0.0001). In a multivariate analysis, full-length hTERT transcripts and International Neuroblastoma Pathology classification grade emerged as the sole independent predictors of event-free survival, with relative risks of 10.0 and 3.9, respectively. The strong statistical correlation of full-length hTERT transcripts with clinical outcome in neuroblastoma suggests that the reverse transcriptase-polymerase chain reaction analysis of hTERT transcripts may be equatable to TA measurements. Because this assay is well suited for archival material, it could become a useful adjunct in evaluating the prognosis of individual neuroblastoma cases.
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PMID:Full-length telomerase reverse transcriptase messenger RNA is an independent prognostic factor in neuroblastoma. 1259 34

The clinicobiological feature of neuroblastoma is enigmatic because spontaneous regression often occurs in early stages of tumors of the patients under 1 year of age, while rapid growth usually occurs in the tumors of the patients over 1 year of age. Such difference in the clinical behavior may be caused by the difference in the pattern of gene expression among the subsets of neuroblastoma. To understand the molecular basis of neuroblastoma biology, we decided to identify the novel genes expressed differentially between favorable and unfavorable neuroblastomas. The oligo-capping cDNA libraries were constructed from different subsets of neuroblastomas. After random selection and DNA sequencing, the differentially expressed genes between favorable and unfavorable neuroblastomas were screened by reverse transcriptase-PCR. The clinical significance of gene expression was evaluated based on the results of Northern blot analysis. We have identified a novel gene Nbla03145 (alpha), also cloned and termed by another group as ECEL1, which encodes a new member of putative zinc-binding metalloendopeptidase (endothelin-converting enzyme) with unknown substrate. We also cloned a COOH-terminally truncated Nbla03145/ECEL1beta which is expressed only in thymus. In primary NBLs, the alpha isoform is more preferentially expressed than the beta isoform. High levels of Nbla03145/ECEL1 expression were significantly correlated with a younger age (p=0.0005), lower stages (p=0.0019), high level of TrkA expression (p</=0.00005), a single copy of MYCN (p<0.00005) and the tumors found by mass screening (p<0.00005). Decreased expression of Nbla03145/ECEL1 mRNA was significantly associated with poor prognosis (log-rank test: p=0.012). The present results have shown that expression of Nbla03145/ECEL1 is a novel prognostic marker of neuroblastoma. Further analysis of the gene may also give a cue to the understanding of the role of endothelin-like signaling in neuroblastoma and to the development of diagnostic and therapeutic strategies against aggressive tumors.
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PMID:High expression of the novel endothelin-converting enzyme genes, Nbla03145/ECEL1alpha and beta, is associated with favorable prognosis in human neuroblastomas. 1263 73

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Histologically, it is subdivided histologically into two main subtypes: alveolar (ARMS) and embryonal (ERMS). ARMS is characterized by t(2;13)(q35;q14) or its variant t(1;13)(p36;q14), which fuse PAX3 and PAX7, respectively, with FKHR to produce chimeric genes. ERMS is frequently associated with loss of heterozygosity of 11p15.5. We investigated seven RMS (three ARMS and four ERMS) by means of cytogenetic, fluorescence in situ hybridization, and molecular analyses, including the study of the main genes implicated in the G1- to S-phase cell cycle transition, and correlated these studies with pathologic findings and clinical outcome. All tumors showed clonal, numerical, and structural chromosomal abnormalities. Two ARMS had the t(2;13)(q35;q14) and the third a PAX7/FKHR fusion, a cryptic t(1;13)(p36;q14), undetected by cytogenetic techniques, but revealed by reverse transcriptase polymerase chain reaction. One ERMS showed a der(11)t(3;11)(p21;p15) as a sole structural anomaly. Gene amplification was seen in four tumors, as double minutes or in the form of homogeneously staining regions. Overexpression of MYCN oncogene was found in two ARMS; N-myc DNA probe detected oncogene amplification located on the double minutes of these cases. Analysis of the regulatory genes responsible for G1- to S-phase transition showed a homozygous deletion of the 9p21 locus genes in a spindle-cell ERMS.
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PMID:Cytogenetic and molecular findings related to rhabdomyosarcoma. An analysis of seven cases. 1285 Mar 75

Neuroblastoma (NBL), one of the most common childhood solid tumors, has a distinct nature in different prognostic subgroups: NBL in patients under 1 year of age usually regresses spontaneously, whereas that in patients over 1 year of age often grows aggressively and eventually kills the patient. To understand the molecular mechanism of biology and tumorigenesis of NBL, we decided to perform a comprehensive approach to unveil the gene expression profiles among the NBL subsets. We constructed the subset-specific oligo-capping cDNA libraries from the primary NBL tissues with favorable (F: stage 1, high expression of TrkA and a single copy of MYCN) and unfavorable (UF: stage 3 or 4, decreased expression of TrkA and MYCN amplification) characteristics and randomly cloned 4654 cDNAs. Among 4243 cDNAs sequenced successfully, 1799 (42.4%) were the genes with unknown function. Excluding the housekeeping genes, an expression profile of each subset was extremely different. To determine the genes expressed differentially between F and UF subsets, we performed semiquantitative reverse transcriptase (RT)-PCR for each of the 1842 independent genes using RNA obtained from 16 F and 16 UF NBLs as template. This revealed that 278 genes were highly expressed in the F subset as compared to the UF one, while, surprisingly, only 27 genes were expressed at higher levels in the UF rather than the F subset. These differentially expressed genes included 194 genes with unknown function. Many of the genes expressed at high levels in the F subset were related to catecholamine biosynthesis, small GTPases, synapse formation, synaptic vesicle transport, and transcription factors regulating differentiation of the neural crest-derived cells. On the other hand, the genes expressed at high levels in the UF subset included transcription factors and/or receptors that might regulate neuronal growth and differentiation. The chromosomal mapping of those genes showed some clusters. Thus, our mass-identification and characterization of the differentially expressed genes between the subsets may become a powerful tool for finding the important genes of NBL as well as developing new diagnostic and therapeutic strategies against aggressive NBL.
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PMID:Expression profiling and characterization of 4200 genes cloned from primary neuroblastomas: identification of 305 genes differentially expressed between favorable and unfavorable subsets. 1293 13

An altered apoptotic response represents a pivotal feature of cancer and is involved in cancerogenesis and resistance to chemotherapy. So far, however, only a few studies have been devoted to survey caspase content in malignant cell lines and primary tumor specimens. In this report, we investigated the expression of two pivotal caspases, 3 and 8, in 63 neuroblastoma specimens by three complementary techniques (i.e., reverse transcriptase polymerase chain reaction, immunoblotting, and immunohistochemistry). We confirmed the frequent absence of caspase 8 expression. Moreover and most important, we demonstrated, for the first time to our knowledge, that a significant percentage of neuroblastomas lack caspase 3 mRNA and protein. Both caspase alterations do not show any correlation with tumor stage and MYCN status. Immunohistochemistry showed a large number of caspase-negative cell islets also present in positive samples. Our findings suggest that the absence of caspases might play an important role in neuroblastoma development and resistance to apoptosis-based treatments.
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PMID:Caspase 3 and 8 deficiency in human neuroblastoma. 1449 95


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