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:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNA biosynthesis catalyzed with DNA-dependent RNA polymerase was demonstrated in the reconstructed system containing isolated lymphocyte nuclei, Mg2+ or Mn2+ salts, ammonium sulphate, in the presence of four nucleosidetriphosphates. Both the Mg2+ and Mn2+-dependent forms of this enzyme were revealed in the nuclei of normal lymphocytes and those of patients suffering from melanoma, carcinoma of the lung and sarcoma. The activities of both forms of RNA-polymerase were greater in the nuclei of the lymphocytes from sick individuals than in the normal analogues. DNA-dependent RNA-polymerase sensitivity to dexamethasone and PHA of the nuclei of lymphocytes obtained from patients with carcinoma of the lung, melanoma, and sarcoma was decreased in comparison with the normal.
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PMID:[Sensitivity of the lymphocyte RNA-synthesizing system of patients with different malignant neoplasms to phytohemagglutinin and dexamethasone]. 85 72

A general transcription factor IID which binds to the TATA box promoter element on RNA polymerase II genes regulates and initiates eukaryotic mRNA synthesis. A quantitative polymerase chain reaction procedure was developed and the human transcription factor IID (hTFIID) transcript was measured in normal human tissues, lung carcinomas, lung carcinoma cell lines, and breast carcinomas. In some normal tissues such as liver, fetal lung, and placenta, relatively low to moderate levels of hTFIID mRNA were detected. In contrast, hTFIID transcript was highly expressed in nearly all solid lung carcinomas and cell lines including both small cell lung cancer and non-small cell lung cancer. hTFIID mRNA was present to a greater extent in small cell lung cancer than non-small cell lung cancer in solid tumors and cell lines. In solid carcinomas of breast, overexpression of hTFIID was also detected. A serum induction study using a serum-starved small cell lung cancer cell line, Lu134BS, indicated hTFIID transcription to be rapidly induced at 15 min following stimulation and its response essentially similar to that of protooncogene, c-fos. These results indicate the involvement of the expression of the general transcription factor hTFIID in lung and breast carcinoma, such as being associated with poor differentiation and high mitotic activity.
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PMID:A general transcription initiation factor, human transcription factor IID, overexpressed in human lung and breast carcinoma and rapidly induced with serum stimulation. 172 4

Insulin-like growth factor (IGF-I) is associated with autocrine and paracrine stimulation for cell growth and development of brain tumor cells. The function of IGF-I in the brain metastatic variant of human lung cancer cells is investigated. The cells used here were derived in vivo with intracarotid injection of human non-small cell lung carcinoma NCI-H226. The tumor was developed as a cultured cell line, H226Br. Unlike the parental cells, H226Br was tumorigenic in nu/nu nude mice. Reverse transcriptase-polymerase chain reaction showed that IGF-I transcript of H226Br is increased compared to that of parental cells. The amount of IGF-I secreted in cultured medium of H226Br is higher than that of cultured parental cells. The IGF-I receptor-specific antibody, alpha IR3, inhibits H226Br growth in serum-free culture. The results established that IGF-I is an autocrine growth regulator for human non-small cell lung cancer cells that progressed to brain.
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PMID:Insulin-like growth factor-I is an autocrine regulator for the brain metastatic variant of a human non-small cell lung cell line. 763 43

A cDNA coding for the beta 4 subunit of murine integrin (m beta 4) has been cloned and sequenced using mRNA from a murine lung carcinoma as the template. The 5' sequence contains two AUG codons, the second of which initiates synthesis of the mature protein. The cDNA sequence has an open reading frame coding for 1748 amino acids (aa), including a signal peptide, cysteine-rich region, serine- and threonine-rich region, transmembrane domain, and a cytoplasmic domain of over 1000 aa. Overall, the deduced m beta 4 aa sequence has 88% identity with the human beta 4 subunit (h beta 4) sequence deduced from the sequence of placental mRNA. Reverse transcriptase-polymerase chain reaction using primers flanking splice sites for two variant forms of h beta 4 transcripts provided evidence for alternate splicing of RNA in the murine spleen and to a lesser extent in the skin, uterus, and thymus but was found at only one of the two alternative sites. Five potential glycosylation sites present in the extracellular domain of h beta 4 are conserved in m beta 4. One tyrosine in the terminal region of the cytoplasmic domain (position 1600) is conserved between m beta 4 and h beta 4 and has the consensus sequence for tyrosine phosphorylation. Finally, a genomic restriction map of m beta 4 shows that the gene is about 40 kb in length. No restriction-fragment length polymorphisms were detected between BALB/c liver and BALB/c lung carcinoma DNA.
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PMID:Sequence of a cDNA encoding the beta 4 subunit of murine integrin. 835 87

Paraneoplastic encephalomyelitis developed as the presenting feature of small-cell lung carcinoma in 3 patients. Two patients with paraneoplastic encephalomyelitis manifested predominantly as subacute sensory neuronopathy did not improve after prednisone treatment and chemotherapy. The third patient had severe axial and limb rigidity and myoclonus, which partially improved after chemotherapy and treatment with intravenous immunoglobulin and prednisone. Serum from each patient immunocytochemically stained the neuropil and to a lesser degree the neuronal cytoplasm in human cerebral and cerebellar cortex. On immunoblots of human neuronal extracts, each patient's serum contained high-titer IgG antibodies reacting with a protein band of apparent molecular mass 125 kd. This autoantibody pattern is indistinguishable from antibodies recently identified in several women with breast carcinoma and stiff-man syndrome. Screening of a human brain complementary DNA expression library with patient serum yielded clones whose sequence is identical to that of the synaptic vesicle-related protein amphiphysin. Reverse transcriptase-polymerase chain reaction demonstrated expression of amphiphysin in 8 of 10 small-cell lung carcinomas and in 5 of 14 breast carcinomas. These observations highlight the clinical and serological heterogeneity of paraneoplastic central nervous system disorders: Patients with a given clinical syndrome may have different antineuronal antibodies, and patients with a given autoantibody specificity have differing clinical presentations.
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PMID:Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis. 861 52

Members of the Janus kinase (Jak) family of protein tyrosine kinases have recently been implicated in the proximal signal transduction events of cytokine receptors. Jak3, a newly discovered member of this family, is believed to be normally limited in its expression to cells of the lymphoid and myeloid lineages. Herein we show that Jak3 is expressed in primary human vascular cells, as well as other non-lymphoid and non-myeloid cell types. Reverse transcriptase-polymerase chain reaction and Northern blot analysis revealed that Jak3 mRNA was expressed at low levels in human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells (HASMC), A549 (human lung carcinoma), and DLD-1 (human colon adenocarcinoma) cells. Higher basal levels of Jak3 mRNA were detected in HMEC-1 (human microvascular cell line) and HepG2 (human hepatocellular carcinoma) cells. Jak3 mRNA expression was induced in HUVEC, HMEC-1, and HASMC by treatment with interleukin-1beta, tumor necrosis factor-alpha, interferon-gamma, and lipopolysaccharide. Jak3 protein was detectable at low levels in untreated HMEC-1, and these levels increased significantly with cytokine treatment. Furthermore, Jak3 protein was phosphorylated upon treatment of these cells with interleukin-4. This work shows that Jak3 is expressed or inducible in human vascular endothelial, vascular smooth muscle, and other non-lymphoid and non-myeloid cells, suggesting a broader role for Jak3 in the cytokine signal transduction of these cells.
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PMID:Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells. 866 78

We established a cell line, designated MS-1, from pleural effusion of a 54-yrs-old male patient with small cell lung carcinoma. MS-1 cells grew as a floating in RPMI-1640 medium supplemented with 10% FBS and the population doubling time was 45 hours. The chromosome number ranged from 49 to 52 and structural abnormalities of 1p+, 3q-, 6p-, 14p+ and 17p+ were observed in all the cells examined. MS-1 cells released PTHrP into the conditioned medium and heterogeneity of the PTHrP molecule produced in the cells was found in the gel permeation chromatography. Expression of the PTHrP gene as well as presence of the PTHrP protein in the cells were confirmed by reverse-transcriptase PCR(RT-PCR) and immunohistochemical staining. These findings indicate that MS-1 cells are derived from human small cell lung carcinoma, which produce PTHrP.
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PMID:[A PTHrP-producing cell line derived from human small cell lung carcinoma]. 918 34

The correlation between the degree of expression of the multidrug resistance-1 (MDR-1) gene and the process of differentiation into non-small-cell, bronchopulmonary carcinoma was studied in vitro and in vivo. For this purpose, a technique for the quantitative analysis of MDR-1 gene expression was developed by competitive reverse-transcriptase polymerase chain reaction. The study of 9 epidermoid carcinomas with various degrees of differentiation did not enable us to establish a correlation in vivo in the patient. However, an in vitro study performed on a non-small-cell lung carcinoma cell line and two of its clones showed that MDR-1 gene expression increased with the degree of differentiation, which was confirmed in vivo when this line was xenografted into nude mice.
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PMID:Correlation between multidrug resistance and the degree of differentiation of non-small-cell bronchopulmonary carcinoma (NSCLC) in vitro and in vivo. 949 74

Expression of facilitative glucose transporter (Glut) isoforms was studied immunohistochemically in lung carcinomas. Glut-1 was expressed in 45 (74%) of 61 lung carcinomas, including 19 (100%) of 19 squamous cell carcinomas. No Glut-1 staining was seen in normal lung epithelium surrounding the tumors. In squamous cell carcinomas and small cell carcinomas, Glut-1 immunostaining was stronger in the central area of tumor cell nests corresponding to the hypoperfused region. Focal staining was seen in 14 (58%) of 24 adenocarcinomas, and positive staining was correlated to lesser differentiation, larger tumor size, and positive lymph node metastasis. Glut-2 was detected in normal airway epithelium, but no positive staining was seen in lung carcinomas. Glut-3 and Glut-4 were not positively stained in normal lung epithelia, but a few lung carcinoma samples showed positive reaction (9 of 61 in Glut-3; 4 of 61 in Glut-4). Glut-4 immunoexpression was seen in regenerating alveolar and bronchiolar epithelia around and in cancer tissues. Glut-5 expression was not detected in normal and tumor tissues. Reverse transcriptase-polymerase chain reaction for Glut-1, Glut-3, and Glut-4 confirmed the expression revealed by immunohistochemical analysis. Overexpression of Glut could enhance uptake of glucose into lung carcinoma cells, and the increased glucose influx could be involved in cell biologic activities.
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PMID:Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage. 983 Dec 15

The murine anti-bombesin monoclonal antibody, 2A11, has been demonstrated to inhibit growth of some small-cell lung cancer (SCLC) cells in nude mice xenografts and in a clinical trial. To determine if the expression of bombesin-like peptides (BLP) and their receptors (GRP-R and NMB-R) correlate with an in vitro response to 2A11, we measured these parameters in seven SCLC cell lines. Gastrin releasing peptide (GRP) mRNA was detected in three of seven cell lines (NCI-H69, NCI-H345, NCI-H510) and neuromedin B (NMB) mRNA was detected in all seven lines using an RNase protection assay (RPA). Immunoreactive BLP was detected in the cell pellets of all lines (range 0.11-59.90 pmol/mg protein) by a solid phase GRP radioimmunoassay (RIA) using 125I-labeled 2A11. RPA detected GRP-receptor mRNA in two cell lines (NCI-H69 and NCI-H345) and NMB-receptor in three lines (NCI-H345, NCI-H510, and NCI-H660). Reverse transcriptase-PCR confirmed the presence of receptor mRNA in these lines and detected NMB-receptor in an additional three lines (NCI-H69, NCI-H82, and NCI-H187). Calcium mobilization in response to BLP stimulation was detected in the six cell lines expressing either GRP-R or NMB-R mRNA but not in NCI-N417, which had no detectable BLP-receptor. 2A11 (5 microg/ml) inhibited colony formation by 26-61% after 2 weeks in all cell lines except NCI-N417. Thus, growth inhibition by 2A11 requires the presence of at least one BLP-receptor. These findings may be useful in selecting patients with SCLC for treatment with 2A11.
Lung Cancer 1998 Sep
PMID:Correlation of expression of bombesin-like peptides and receptors with growth inhibition by an anti-bombesin antibody in small-cell lung cancer cell lines. 985 94


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