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 have previously shown that neoplastic cells of human breast cancers, leukemias, lymphomas, and sarcomas contain particles similar to the viruses that have been established as etiologic agents of these diseases in mice. The present paper concerns tumors of the central nervous system for which no suitable animal model or corresponding virus exists. Nevertheless, using the simultaneous detection test, we showed that human brain tumors contain 70S RNA and RNA-directed DNA polymerase encapsulated in a particulate component possessing a density of 1.17 g/ml. These particles satisfy the three diagnostic criteria that characterize RNA tumor viruses of animals. 24 Out of 26 (92%) of the most malignant (glioblastoma and medulloblastoma) brain tumors examined contained these virus-like entities.
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PMID:Particles with RNA of high molecular weight and RNA-directed DNA polymerase in human brain tumors. 412 27

Short-term cultures of cells from human rain tumours have been reported to synthesise RNA particles of density in the range characteristic of C type RNA retroviruses, with associated DNA polymerase activity. Fresh tumour cells obtained from 6 children with astrocytoma and 7 children with medulloblastoma, together with one sample of normal brain tissue and normal leukocytes from brain tumour patients were assayed by several characteristics for the primate retrovirus. 1 or 6 (17%) astrocytomas and 4 of 7 (57%) medulloblastomas released RNA particles which banded in sucrose gradients at a density of 1.16-1.18 g/cm3 together with a short segment of DNA, which was eliminated by prior ribonuclease treatment and two proteins of 28k and 16k daltons. These findings were compatible with the presence of a primate retrovirus. Immune coprecipitation of 125I-labelled proteins from the 1.16-1.18 g/cm3 gradient region failed to show any reactivity with antisera to p28 core antigens or the p70 reverse transcriptase antigens of simian sarcoma virus, baboon endogenous virus or Mason Pfizer virus. Assays for DNA polymerase activity in culture supernatant fluid showed only a low amount of activity with template preferences not characteristic of the retroviral reverse transcriptase enzyme.
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PMID:Children's brain tumour cells produce RNA particles with incomplete retrovirus characteristics. 628 9

The cell-surface receptor for hyaluronic acid, CD44, is expressed by both normal and malignant cells. Numerous CD44 isoforms have recently been identified that are derived by alternative ribonucleic acid splicing. The expression of some CD44 isoforms has been shown to be involved in tumor progression and metastatic spread in a rat carcinoma model and in human carcinomas. In the present study, CD44 isoform expression was evaluated by reverse transcriptase-polymerase chain reaction (PCR) analysis in frozen sections derived from three samples of normal brain tissue and from 40 brain tumors, including samples of glioblastoma multiforme, anaplastic astrocytoma, low-grade astrocytoma, cerebral primitive neuroectodermal tumor, medulloblastoma, metastatic colon carcinoma, and metastatic melanoma. Normal brain tissue adjacent to the tumors was also examined in 14 of 18 glioblastomas. In all normal brain and tumor samples, with the exception of metastases from colon carcinoma, PCR analysis demonstrated one prominent product that corresponded to the CD44H hematopoietic form of CD44. Metastases from colon carcinoma demonstrated two prominent PCR amplification products corresponding to CD44H and CD44R1. These results suggest that CD44H is the predominant isoform of this protein in normal human brain tissue and in human neuroectodermal tumors of varying degrees of malignancy. The ability of CD44H to mediate tumor cell motility and invasiveness (in contrast to CD44R1) suggests that the CD44 alternative splicing pattern of neuroectoderm-derived tumors may enhance their local biological aggressiveness and intracerebral spread. The lack of expression of larger molecular weight CD44 variants by primary brain tumors may also partially explain why these tumors rarely metastasize to distant sites.
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PMID:Alternative RNA splicing of the hyaluronic acid receptor CD44 in the normal human brain and in brain tumors. 753 36

We evaluated expression of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor (GluR) genes by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting in nine established cell lines: rat CG-4 (oligodendroglial lineage) and RINm5F insulinoma cells; human CHP134, SMS-KCNR, SKNSH, and Nb69 neuroblastoma cells; and human D384Med, D425Med, and D458Med medulloblastoma cells. CG-4 expressed mRNAs encoding GluR2-7, KA-1, and KA-2 non-NMDA GluR (Yoshioka et al.: J Neurochem 64:2442-2448, 1995) and NR1 (NMDAR1) and NR2D NMDA GluR. After differentiation to oligodendrocyte-like cells, CG-4 also expressed NR2B mRNA. Rat insulinoma cells expressed GluR5 and KA-2 non-NMDA and NR1 and NR2D NMDA GluR mRNAs. The four human neuroblastoma lines all expressed mRNAs encoding GluR2-4, 6, 7 and KA-1 non-NMDA and NR1 NMDA GluR, and the three human medulloblastoma cell lines all expressed mRNAs encoding GluR1, 6 and KA-1, but none of the NMDA GluRs. Whereas CG-4 is susceptible to kainate excitotoxicity, treatment of insulinoma, neuroblastoma, and medulloblastoma lines with L-glutamate, kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), or NMDA failed to cause cell damage or to augment 45Ca2+ influx. Thus, despite expressing a variety of non-NMDA and NMDA GluR genes, the human neuroblastoma and medulloblastoma and rat insulinoma lines failed to assemble Ca(2+)-permeable NMDA or non-NMDA GluR channels. This failure confers protection against excitotoxicity and may contribute to progression of tumors of these types.
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PMID:Expression of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor genes in neuroblastoma, medulloblastoma, and other cells lines. 891 93

Medulloblastoma is a pediatric malignancy, which arises in cerebellum. The neuropeptide somatostatin (SS-14) is a neuromodulator and growth regulator in the developing cerebellum. SS-14 has previously been demonstrated in medulloblastomas with immunohistochemical techniques, but somatostatin receptor (sst) expression is less well understood. We analyzed somatostatin and sst subtype expression (sst1-5) in central primitive neuroectodermal tumors (cPNET), including 23 medulloblastomas, 6 supratentorial PNET, and 10 cPNET cell lines. The expression of SS-14 and sst genes in cPNET was compared with expression of these genes in 17 tumors of the Ewing's sarcoma family of tumors using reverse transcriptase-PCR, Southern hybridization, quantitative in vitro receptor autoradiography, and competitive membrane binding assays. The sst1 subtype was expressed in similar frequency in cPNET (83%) and Ewing's sarcoma family of tumors (71%). Nine of the 10 cell lines and 76% of the cPNET expressed mRNA for sst2 compared with 35% of the Ewing's sarcoma family of tumors. High-affinity binding of SS-14 was demonstrated in cPNET by quantitative autoradiography as well as by competitive binding assays. The cPNET cell line D283 Med bound SS-14 and octreotide with high affinity; SS-14 inhibited proliferation of D283 Med cells as measured by a decrease in [3H]thymidine uptake. We conclude that both sst1 and sst2 are highly expressed in cPNET and suggest that somatostatin may regulate proliferation and differentiation in these developmental tumors.
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PMID:High expression of somatostatin receptor subtype 2 (sst2) in medulloblastoma: implications for diagnosis and therapy. 1023 68

Similarities between primitive neuroectodermal tumors and central nervous system (CNS) progenitor cells have evoked interest in the response of these tumors to endogenous growth factors. The bone morphogenetic proteins (BMPs) have recently been found to regulate survival and differentiation of CNS progenitor cell populations. In this study, we investigated the effects of BMP-2, BMP-4, and BMP-6 on the undifferentiated cerebellar primitive neuroectodermal tumor or medulloblastoma cell line DAOY. Analysis by reverse transcriptase-polymerase chain reaction showed that mRNAs for type IA and type II BMP receptors were present in control cultures. In cultures treated with BMP-2, mRNAs for BMP receptor type IB and the activin R-I receptor became evident. Cultures were analyzed for total cell counts, proliferating cell nuclear antigen (PCNA), and apoptotic DNA fragmentation. There was a significant increase in total cell number in the BMP-2 and BMP-4 treatment groups, without any change in PCNA reactivity, and a dramatic decrease in the proportion of apoptotic nuclei at concentrations of BMP-2 and BMP-4 above 5 ng/ml (P<0.001). These effects were not observed with BMP-6, TGF-beta1 or GDNF. These results suggest that the increase in total cell number is due to the attenuation of apoptosis by BMP-2 and BMP-4. The anti-apoptotic effect of BMP-2 and BMP-4 on this neuroectodermal cell line has potential clinical implications for neuroectodermal tumors.
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PMID:Bone morphogenetic proteins-2 and -4 attenuate apoptosis in a cerebellar primitive neuroectodermal tumor cell line. 1033 54

Primitive neuroectodermal tumors (PNET) occur either in the central nervous system (CNS; central PNET, cPNET) or in the peripheral sites (peripheral PNET, pPNET). Recent molecular approaches have been defining a new concept of PNET, that is, the pPNET including Ewing's sarcoma (ES) which expresses MIC2 glycoprotein and shows the specific chimeric gene of EWS-FLI1. The expression of MIC2 and the genetic rearrangement of EWS-FLI1 are considered to be highly specific to the pPNET/ES. This study examined the expression of MIC2 and EWS-FLI1 gene by means of immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) on various small round cell tumors originating in the CNS or non-CNS organs. All peripheral PNET tested expressed MIC2 and were positive for EWS-FLI1 (11/11). In contrast, all cPNET and other blastic CNS tumors were negative for MIC2: medulloblastoma (0/3), cerebral PNET (0/2), spinal PNET (0/2), glioblastoma (0/2), retinoblastoma (0/3), and pineoblastoma (0/2). These MIC2-negative tumors were also negative for the chimeric gene product of EWS-FLI1. Interestingly, one PNET originating in the intracranial dura mater was positive for both MIC2 and EWS-FLI1 fusion gene. The results indicate that cPNET lacks any genetic or protein markers, except for a meningeal PNET which falls into the same phenotypic spectrum of pPNET.
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PMID:Alternative EWS-FLI1 fusion gene and MIC2 expression in peripheral and central primitive neuroectodermal tumors. 1130 41

Upon binding of tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), the agonistic TRAIL receptors DR4 and DR5 activate caspase-8 leading to apoptosis. In primitive neuroectodermal brain tumour (PNET) cell lines, TRAIL-induced apoptosis was recently shown to correlate with caspase-8 mRNA expression (Grotzer MA, Eggert A, Zuzak TJ, et al. Oncogene 2000, 19, 4604-4610). In this study, we analysed the expression of the TRAIL death pathway in 27 primary PNET/medulloblastoma. As shown by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), all PNET/medulloblastoma evaluated expressed DR5, the adapter protein FADD and caspase-3, but only 48% expressed caspase-8. The mRNA expression of caspase-8 was significantly lower in primary PNET/medulloblastoma compared with normal brain samples. PCR revealed >75% methylation of the caspase-8 promoter region in three of seven PNET cell lines and in 55% of the primary PNET/medulloblastoma evaluated. In the PNET cell lines, the methylation status correlated with the caspase-8 mRNA expression. We conclude that loss of caspase-8 gene expression is common in PNET/medulloblastoma suggesting that suppression of death receptor induced apoptosis may play an important role in the pathogenesis of this common childhood brain tumour.
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PMID:Loss of caspase-8 mRNA expression is common in childhood primitive neuroectodermal brain tumour/medulloblastoma. 1182 14

NELL1 and NELL2 encode cysteine-rich amino acid sequences including six epidermal growth factor-like motifs, which contain signal peptides at the N-terminals. The deduced amino acid sequences of both genes are 55% identical and their cysteine stretch structures are conserved. NELL1 is expressed in the brain and kidney, whereas NELL2 is expressed specifically in the brain. The cell lineage expressing NELLs in the nervous system was investigated in established cell lines and central nervous system tumor tissues obtained from patients by Northern blot and reverse transcriptase-polymerase chain reaction analyses. NELL1 and NELL2 were predominantly expressed in neuroblastoma cell lines and little expressed in glioblastoma cell lines. NELL1 and NELL2 were also expressed in central neurocytoma, medulloblastoma, and some astrocytic tumors. Immunohistochemical analysis revealed that NELL2 protein was localized in the cytoplasm of neurons. These results suggest that NELL2 is predominantly expressed in the neuronal cell lineage in the human nervous system. NELL1 is expressed mainly in tumors in the neuronal cell lineage.
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PMID:Brain specific human genes, NELL1 and NELL2, are predominantly expressed in neuroblastoma and other embryonal neuroepithelial tumors. 1180 83

Gonadotropin releasing hormone-I (GnRH-I), a decapeptide serves as a key regulator of reproduction. Recently, several groups have identified in the mammalian brain a second form of GnRH, of unknown function, designated GnRH-II. The human neuronal medulloblastoma cells (TE-671) were recently demonstrated to express the two forms of GnRH (GnRH-I and GnRH-II). We used this cell line, as a model system, to investigate the regulation of human GnRH-I and GnRH-II genes by estrogen. Estrogen is one of the principal regulators of GnRH-I in hypothalamic neurons, acting as a classic homeostatic feedback molecule between the gonads and the brain. In this study, we investigated the regulation of the two GnRH forms by estrogen, in the human neuronal cell line TE-671. We demonstrate, for the first time, that the hGnRH-II and hGnRH-I genes are differentially regulated by estrogen. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern hybridization, we found that estrogen increases endogenous hGnRH-II mRNA levels and decreases endogenous hGnRH-I mRNA levels. Furthermore, we found these effects to be promoter-mediated. We cloned the hGnRH-I and hGnRH-II promoter constructs upstream to a luciferase reporter plasmid, and cotransfected these constructs with an estrogen receptor alpha into the TE-671 neuronal cells. Luciferase activity of GnRH promoter constructs treated with estrogen demonstrates that the differential regulation of the GnRH genes by estrogen is mediated at the transcription level.
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PMID:The transcription of the hGnRH-I and hGnRH-II genes in human neuronal cells is differentially regulated by estrogen. 1193 51


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