Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The capacity of brain tumor samples to synthesize pituitary adenylate cyclase activating polypeptide (PACAP) was evaluated by the reverse transcriptase-polymerase chain reaction technique (RT-PCR). The expression of PACAP receptors was assessed by a combination of RT-PCR techniques, conventional binding techniques, and also by the ability of PACAP to stimulate adenylate cyclase activity. A weak PACAP mRNA and PACAP receptor mRNA expression was detected in only 3 of 16 meningiomas. A weak PACAP-stimulated adenylate cyclase activity (+20%) was detected in 10 of the 16 samples but binding of labeled PACAP was never observed. In the 16 gliomas studied (including two oligodendrogliomas and two ependymomas), PACAP mRNA was identified in 13 samples and PACAP receptor mRNA in 15 samples. PACAP receptors were identified in all the samples by binding studies and/or by PACAP stimulation of the adenylate cyclase activity. PACAP mRNA was never detected in pituitary adenomas (three prolactinomas, two mixed PRL-GH-producing tumors, three GH-secreting tumors, three gonadotrophinomas, one ACTH-producing tumor, two nonsecreting tumors) whereas PACAP receptor mRNA was highly expressed in all the tumors except prolactinomas, where it was at the limit of detection, confirming the binding and adenylate cyclase activation results. Thus, it is unlikely that the neuropeptide PACAP could influence meningioma's cell growth; PACAP secreted from extratumoral areas may influence pituitary tumors and PACAP could participate to gliomas development.
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PMID:Expression of pituitary adenylate cyclase activating polypeptide and receptors in human brain tumors. 747 7

Adenoviral vectors have recently been shown to effectively deliver genes into a variety of tissues. Since these vectors have some advantages over the more extensively investigated retroviruses, we studied the effect of two replication-defective adenovectors bearing human wild type tumor suppressor gene p53 (Adp53) and Escherichia coli beta-galactosidase gene (AdLacZ) on 9L glioma cells. Successful in vitro gene transfer was shown by DNA polymerase chain reaction (PCR), and expression was confirmed by reverse transcriptase RNA PCR and Western blot analyses. Transduction of 9L cells with the Adp53 inhibited cell growth and induced phenotypic changes consistent with cell death at low titers, while AdLacZ caused cytopathic changes only at high titers. Stereotactic injection of AdLacZ (10(7) plaque forming units) into tumor bed stained 25 to 30% of tumor cells at the site of vector delivery. Injection of Adp53 (10(7) plaque forming units), but not AdLacZ (controls), into established 4-day old 9L glioma brain tumors decreased tumor volume by 40% after 14 days. As a step toward gene therapy of brain tumors using replication-defective adenoviruses, these data support the use of tumor suppressor gene transfer for in vivo treatment of whole animal brain tumor models.
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PMID:Adenovirus-mediated p53 gene delivery inhibits 9L glioma growth in rats. 764 77

Insulin-like growth factor 1 (IGF-1) is involved in the regulation of brain development and has been suggested as an autocrine stimulator of brain tumor cell proliferation. This study demonstrates the expression of IGF-1 in tumor tissue from human gliomas and one esthesioneuroblastoma. Using immunohistochemistry, expression of an IGF-1-like peptide was localized in tumor cells of 6 of the 9 gliomas examined as well as the esthesioneuroblastoma. From one anaplastic oligodendroglioma (which showed strong IGF-1 immunostaining) the IGF-1 transcripts were characterized after isolation of mRNA followed by amplification using the reverse transcriptase-polymerase chain reaction. Two IGF-1 complementary DNAs resulting from alternative splicing of the IGF-1 primary transcript were identified. These transcripts encode two different precursor proteins which correspond to Ea IGF-1 and Eb IGF-1. The significance of IGF-1 alternative mRNA splicing pathways remains to be determined.
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PMID:Characterization of insulin-like growth factor 1 in human primary brain tumors. 849 8

Gonadotropin-releasing hormone (GnRH) is encoded by the proGnRH gene which contains four exons and three introns. In this study, two immortalized GnRH-expressing cell lines (Gn11 and NLT) were characterized. The NLT and Gn11 cells, derived from a same brain tumor in a transgenic mouse, display neuronal morphology and neuron-specific markers. However, NLT cells secrete much higher levels of GnRH than Gn11 cells. To delineate the mechanism underlying this difference, reverse transcriptase-polymerase chain reaction and RNase protection assays were performed to examine proGnRH gene expression. While the mature proGnRH mRNA was predominately expressed in NLT cells, Gn11 cells express an abundant short transcript. Sequence analysis revealed that this short transcript contains exons 1, 3, and 4, but not exon 2, which encodes the GnRH decapeptide. RNase protection assays demonstrated that NLT cells express much higher levels of mature proGnRH mRNA than Gn11 cells. The lower level of GnRH secreting capacity in Gn11 cells is due, in part, to decreased expression of mature proGnRH mRNA. When proGnRH gene expression in the mouse brain was examined, the same short splicing variant was observed in the olfactory area and preoptic area-anterior hypothalamus. But the prevalent transcript in these regions was the mature proGnRH mRNA. In contrast, only the mature proGnRH mRNA was found in the caudal hypothalamus. These results suggest that alternative splicing may be one of the mechanisms regulating proGnRH gene expression in the animal brain.
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PMID:An alternative gonadotropin-releasing hormone (GnRH) RNA splicing product found in cultured GnRH neurons and mouse hypothalamus. 913 17

Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) has been proposed to mediate the cellular uptake and clearance of inactivated protease-inhibitor complexes in regulating proteinase activity at the cell surface, which is necessary for cellular migration and invasive processes. In this study, we investigated the presence of both LRP and urokinase-type plasminogen activator receptor (uPAR) in glioblastoma by reverse transcriptase-polymerase chain reaction (RT-PCR), and the cellular localization of LRP in glioblastoma tissues by immunohistochemical analysis. LRP mRNA was frequently expressed in glioblastomas and anaplastic astrocytomas compared with low-grade astrocytomas by RT-PCR analysis, and was well correlated with uPAR expression. The immunohistochemistry of LRP on sequential frozen sections showed that neoplastic glial cells and endothelial cells of glioblastomas exhibited intense LRP immunoreactivity, whereas LRP was almost undetectable in low-grade astrocytomas or in normal glial cells and endothelial cells of normal brain tissue. Glioblastomas from 11 patients in which the expression of LRP mRNA was observed by PCR displayed strong to moderate LRP immunoreactivity, with predominantly diffuse cytoplasmic and cell-surface localization. In normal brain tissues, LRP immunoreactivity was identified in the pyramidal neurons of the cerebral cortex. These results indicate that LRP is present both in the cellular cytoplasm and on the cell surface of glioblastomas with an increased expression of uPAR. Altered LRP expression might contribute to the stimulation of cell-surface proteolytic activity that in turn facilitates the invasiveness of glioblastoma in vivo.
Brain Tumor Pathol 1998
PMID:Expression and cellular localization of low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in human glioblastoma in vivo. 987 60

A two-step strategy was developed consisting of differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) with cultured normal human fetal astrocytes and U-373MG glioma cells followed by reverse Northern analysis of normal brain and primary tumor tissues. hu-dek, alpha-NAC, ribosomal proteins L7a and L35a, and five novel genes were identified. Since none of these genes has been previously shown to be associated with malignant brain tumor formation, this approach may be useful to identify novel targets for the diagnosis and treatment of brain tumors.
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PMID:The identification of novel therapeutic targets for the treatment of malignant brain tumors. 1088 Jul 69

Our previous study showed that high-grade astrocytomas often expressed high interleukin (IL)-1beta production. Coexpression of IL-1beta and IL-6 has been found in a number of glioma samples and glioma cell lines. To characterize the expression of IL-6 in the human glioma microenvironment, we investigated surgically excised human gliomas, human glioblastoma xenografts, and human glioblastoma cell lines using the reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). In the 29 primary gliomas, transcripts of IL-6 were less frequently detectable (55.6%) than those of IL-1beta (72.4%) or those of IL-10, IL-8, or IL-1alpha (>80% each). As for IL-6 gene expression, little or no transcription was observed in low-grade astrocytomas, oligodendroglial tumors, and 1 ependymoma. Strong IL-6 gene expression was found in only 5 of 9 glioblastomas. Immunohistochemically, IL-6 antigen was localized in the tumor cells and macrophages in 4 of 7 glioblastomas. In 3 glioblastomas transplanted into nude mice, both IL-1beta and IL-6 were detected only in 1, but othercytokines (IL-8, IL-10, and IL-1alpha) were detected in all 3 xenografts by RT-PCR. Two cell lines both showed IL-6 expression at the mRNA level, and in a cell line with a high level of IL-6 and IL-1beta transcripts, significant production of IL-6 was observed by IHC and ELISA. We concluded that IL-6 produced in tumor tissue may be involved in tumor progression in some glioblastomas, but not in low-grade astrocytomas and oligodendroglial tumors, and that IL-6 gene expression is closely correlated with IL-1beta expression in biopsy tissue, xenografts, and cultures of human gliomas.
Brain Tumor Pathol 2001
PMID:Analysis of interleukin-6 gene expression in primary human gliomas, glioblastoma xenografts, and glioblastoma cell lines. 1151 69

With the use of RT-PCR (reverse transcriptase-polymerase chain reaction), Northern blot analysis, and Western blot analysis, seven primary brain lymphomas were examined for the state of the MMACI tumor suppressor gene. Nucleotide analysis of RT-PCR clones revealed no abnormality in the MMAC1 coding sequence in each case. Although Northern blot revealed variation among cases in the signal intensities for MMAC1 mRNA, Western blot revealed a distinct MMAC1 protein band in all cases, suggesting that the actual MMAC1 expressions were similar. In Western blot analysis of phosphorylated Akt (p-Akt), which is regulated positively by PI3K (phosphoinositide-3 kinase) and negatively by MMAC1, all the lymphomas revealed an Akt band but not a p-Akt band, suggesting that the MMAC1 phosphatase activity was maintained in each case. These findings suggest that the MMAC1 gene is normal in its coding sequence, gene expression, and phosphatase activity in the lymphomas. Thus, unlike the p16 and p15 tumor suppressor genes, which are frequently deleted and inactivated in brain lymphoma and represent a striking contrast to systemic lymphoma, MMAC1 may not play an important role in carcinogenesis in this tumor, as in the systemic counterpart.
Brain Tumor Pathol 2001
PMID:Primary malignant lymphoma of the brain: analysis of MMAC1 (PTEN) tumor suppressor gene. 1190 70

Presently, there is no effective treatment for glioblastoma, the most malignant and common brain tumor. Growth factors are potential targets for therapeutic strategies because they are essential for tumor growth and progression. Peptidylglycine alpha-amidating monooxygenase is the enzyme producing alpha-amidated bioactive peptides from their inactive glycine-extended precursors. The high expression of peptidylglycine alpha-amidating monooxygenase mRNA in glioblastoma and glioma cell lines points to the involvement of alpha-amidated peptides in tumorigenic growth processes in the brain. After screening of amidated peptides, it was found that human glioblastoma cell lines express high levels of adrenomedullin (AM) mRNA, and that immunoreactive AM is released into the culture medium. AM is a multifunctional regulatory peptide with mitogenic and angiogenic capabilities among others. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis showed that AM mRNA was correlated to the tumor type and grade, with high expression in all glioblastomas analyzed, whereas a low expression was found in anaplastic astrocytomas and barely detectable levels in low-grade astrocytomas and oligodendrogliomas. In the present study we also demonstrate the presence of mRNA encoding the putative AM receptors, calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CRLR/RAMP2; CRLR/RAMP3) in both glioma tissues and glioblastoma cell lines and further show that exogenously added AM can stimulate the growth of these glioblastoma cells in vitro. These findings suggest that AM may function as an autocrine growth factor for glioblastoma cells. One way to test the autocrine hypothesis is to interrupt the function of the endogenously produced AM. Herein, we demonstrate that a polyclonal antibody specific to AM, blocks the binding of the hormone to its cellular receptors and decreases by 33% (P < 0.001) the growth of U87 glioblastoma cells in vitro. Intratumoral administration of the anti-AM antibody resulted in a 70% (P < 0.001) reduction in subcutaneous U87 xenograft weight 21 days after treatment. Furthermore, the density of vessels was decreased in the antibody-treated tumors. These findings support that AM may function as a potent autocrine/paracrine growth factor for human glioblastomas and demonstrate that inhibition of the action of AM (produced by tumor cells) may suppress tumor growth in vivo.
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PMID:Neutralization of adrenomedullin inhibits the growth of human glioblastoma cell lines in vitro and suppresses tumor xenograft growth in vivo. 1194 13

Brain tumor formation and growth is accompanied by the proliferation and infiltration of blood capillaries. The phenotypes of endothelial cells that make up capillaries are known to differ not only in the tissues in which endothelial cells are located but also as a result of the microenvironment to which they are exposed. For this reason, primary cultures of brain endothelial cells were isolated from human brain tumors removed by surgery and compared with cells from normal tissue. The primary confluent monolayers that grew out of isolated capillary fragments consisted of closely associated, elongated, fusiform-shaped cells. But brain tumor-derived endothelial cells in culture exhibited significantly less expression of endothelial-specific Factor VIII-related antigen compared with cells isolated from normal tissue. Cultured cells that exhibited binding of Ulex europaeus lectin were shown to take up Dil-Ac-Ldl and formed continuous monolayers that were joined together by tight junctions. The cells also exhibited characteristics of the cells of the brain microvasculature in vitro as seen by the presence of large numbers of mitochondria and few pinocytotic vesicles and by the absence of Weibel-Palade bodies within the cells. The expression of vascular cell adhesion molecule-1, E-Selectin, and the tight junction associated protein ZO-1 but not intercellular adhesion molecule-1 was demonstrated by immunohistological staining or reverse transcriptase-polymerase chain reaction methodologies. Comparative studies of these endothelial cells with endothelial cells from normal tissue will be useful for determining and understanding how the blood-brain barrier differs and functions in tumor and healthy tissues and may lead to strategies for brain tumor therapeutic approaches.
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PMID:Isolation and molecular characterization of brain microvascular endothelial cells from human brain tumors. 1241 24


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