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)

In the present study we characterized the responses of the cell line HST-alpha, stably transformed by a secreted form of human fibroblast growth factor-1 (acidic FGF) gene, and its parental NIH 3T3 cell line to recombinant murine (rMu) TNF-alpha. Treatment of HST-alpha cells with rMu TNF-alpha can significantly reduce the number of foci formed in the in vitro transformation assay. In the presence of the RNA polymerase inhibitor actinomycin-D, the transformed HST-alpha cell is more susceptible to the cytotoxicity of rMu TNF-alpha than is its parental NIH 3T3 cell. The median lethal concentrations (LC50) of rMu TNF-alpha to HST-alpha cell and NIH 3T3 cell were 0.35 ng/ml and 4.56 ng/ml respectively. These results demonstrated that the introduction of a single oncogene or a growth factor gene to a cell can change the cell's response to cytokines.
Cancer Lett 1995 Feb 10
PMID:Effect of tumor necrosis factor-alpha on a cell line transformed by a secreted form of human fibroblast growth factor-1 gene and on its parental cell line. 753 57

Using immunostaining, immunoblot, reverse-transcriptase polymerase chain reaction and Southern blot, we found that expressions of CD44 isoforms and E-cadherin were very closely linked and were correlated with the differentiation status in human urothelial cell lines and clinical specimens of transitional cell carcinoma. Normal urothelium, well to moderately differentiated cell lines and surgical samples expressed E-cadherin and large CD44 isoforms containing exon v6, which was pivotal in metastasis of rat pancreatic cell line model. Poorly differentiated cell lines and surgical samples, were E-cadherin-negative and expressed primarily standard form CD44, which did not contain exon v6. We concluded that CD44v6 isoforms and E-cadherin were both down-regulated during the carcinogenesis of urothelium. The large exon v6 containing CD44 isoforms were readily detected in normal urothelium, therefore, were not likely linked to cancer metastasis. E-cadherin and CD44v6 may be used as differentiation markers for human urothelial tumors. Immunohistochemical study solely with antibody against epitopes encoded by exon v6 alone is not informative enough as other alternatively spliced exons may change the function of CD44v6 isoforms.
Cancer Lett 1995 Feb 10
PMID:Correlation of expression of CD44 isoforms and E-cadherin with differentiation in human urothelial cell lines and transitional cell carcinoma. 753 58

Ornithine decarboxylase (ODC) plays an important role in cell proliferation. Its expression is tightly regulated at the mRNA and protein levels and is found to be deregulated in various malignancies. The rapid and dramatic induction of cellular ODC mRNA upon serum addition raised the possibility that a transcriptional attenuation mechanism may be involved in the regulation of ODC gene expression. Using transcription in HeLa nuclear extract and isolated transcription complexes, we have identified two sites of transcription arrest downstream to the transcription start site: Attenuator 1 (Att.1) located at +220, near two repeats of a USF/Myc-Max binding consensus sequence and attenuator 2 (Att.2) located at +1590 near a long stretch of T-residues. The two attenuators exhibit distinct properties as revealed by elongation of briefly initiated and partially purified transcription complexes: Att.1 serves as a transient pause site while arrest at Att.2 is more prolonged. The arrest at both attenuators is modulated by the general elongation factor TFIIS. In a promoter independent transcription system, using partially purified RNA polymerase II, only Att.2 was recognized efficiently. This suggests that the recognition of Att.2 is an intrinsic property of the polymerase while Att.1 recognition has to be facilitated by an auxiliary factor/s.
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PMID:Transcription elongation of the murine ornithine decarboxylase (ODC) gene is regulated in vitro at two downstream elements by different attenuation mechanisms. 753 63

The growth of a panel of 22 different human tumor, leukemia, and lymphoma cell lines was examined in a human tumor cloning assay in agar or methylcellulose and a tritiated thymidine uptake assay. The cultures were performed in the absence or presence of increasing concentrations (0.5-500 ng/ml) of nerve growth factor (NGF). The growth of 17 of the 22 cell lines was not significantly and reproducibly affected by NGF. There was minor (1.2-fold) but reproducible stimulation of clonal growth in one glioblastoma cell line (86-HG-39) by NGF, but in this cell line NGF induced no growth modulation in a tritiated thymidine uptake assay. However, clonal growth of another glioblastoma cell line (87-HG-31) and all three lung cancer cell lines tested (HTB 119, HTB 120, CCL 185) could be stimulated up to 3-fold by NGF with a dose-response relationship for the growth factor. Growth stimulation by NGF could be completely reversed by neutralizing anti-NGF antibody and by the tyrosine kinase inhibitor genistein. Evaluation of secondary plating efficiency revealed the stimulation of colony formation as representing self-renewal and not terminal differentiation. Reverse transcriptase-PCR experiments in the five responding cell lines showed expression of both low-affinity NGF receptor (glycoprotein 75) and c-trk transcripts on the mRNA level. Of the five responding cell lines, only 86-HG-39, the cell line with the lowest responsiveness, revealed low-affinity NGF receptor on the protein level; the other four cell lines with high responsiveness, including the three lung cancer cell lines, expressed no low-affinity NGF receptor as shown by fluorescence-activated cell sorter analysis and immunoprecipitation using the ME 20.4 antibody. Immunoprecipitation using anti-trk antibodies was negative in all five responding cell lines. However, binding studies with iodinated NGF showed only low-affinity binding on the 86-HG-39 cell line and only high-affinity binding on the high-responder cell lines CCL 185 and 87-HG-31. In summary, our data suggest that NGF can be operative in stimulation of clonal growth of malignant tumor cells. High-affinity but not low-affinity binding sites mediate signal transduction for clonal growth and signaling involves tyrosine kinase activity.
Cancer Res 1995 May 15
PMID:Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling. 753 48

The genes CDKN2B (MTS2) and CDKN2 (MTS1) encoding the proteins p15 and p16 are both located on chromosomal band 9p21, a locus at which frequent homozygous and heterozygous deletions occur in many primary human tumors, including esophageal carcinoma. CDKN2 and CDKN2B belong to a family of cyclin-dependent kinase 4 inhibitors (INK41) and control cell proliferation during the G1 phase of the cell cycle. Their inactivation may contribute to uncontrolled growth in human cancers. To investigate whether CDKN2B and CDKN2 are involved in esophageal tumorigenesis, we studied homozygous deletion, intragenic mutation, and messenger RNA (mRNA) expression of CDKN2 and CDKN2B in nine esophageal squamous cancer cell lines. Polymerase chain reaction (PCR) amplification revealed that five of the nine cell lines (55%) manifested homozygous deletions of CDKN2B, CDKN2, and/or flanking loci on chromosomal band 9p21. Reverse transcriptase-PCR (RT-PCR) was used to examine CDKN2 and CDKN2B mRNA in the nine cell lines. Lack of CDKN2 and CDKN2B mRNA correlated perfectly with homozygous deletion involving these genes. No subtle intragenic mutations of CDKN2B or CDKN2 were detected by DNA sequencing of their entire coding sequences in any cell lines lacking homozygous deletion. Two of the cell lines manifested homozygous deletions excluding CDKN2; one of these two deletions also excluded CDKN2B. These results suggest that inactivation of CDKN2B and CDKN2 may contribute to the malignant phenotype in esophageal cells and that homozygous deletion may be the predominant mechanism for inactivation of CDKN2B and CDKN2. Alternatively, a gene or genes adjacent to CDKN2B/CDKN2 may constitute the target(s) of deletion at this locus.
Genes Chromosomes Cancer 1995 Aug
PMID:Genomic DNA and messenger RNA expression alterations of the CDKN2B and CDKN2 genes in esophageal squamous carcinoma cell lines. 754 37

Bone and soft tissue sarcomas are diagnostically challenging. Recognition of specific cytogenetic abnormalities in these neoplasms has significantly reduced some of the associated difficulties and has provided valuable information on histopathogenesis. Commonly, translocations involving an exchange of chromosomal material and creation of novel chimeric genes are detected. These fusion genes frequently function as aberrant transcription factors that contribute to sarcomagenesis. New studies indicate that less commonly occurring variant fusion genes are also present in some tumors, eg, Ewing's sarcoma and alveolar rhabdomyosarcoma. The clinical consequences, if any, of these variant hybrids are not yet known. Reverse transcriptase polymerase chain reaction and are useful approaches in detecting these transcripts. In addition to translocations, supernumerary ring chromosomes are often encountered in sarcomas, particularly those of intermediate or borderline malignancy. Traditional fluorescence in situ hybridization, and recently, comparative genomic hybridization have uncovered the chromosomal composition of these rings as well as some associated gene amplifications in well-differentiated liposarcoma and dermatofibrosarcoma protuberans.
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PMID:Cytogenetics and experimental models of sarcomas. 757 81

Ovarian-carcinoma cell lines (OVCAR3, IGROVI, OVCA432, SW626 and SKOV3), grown in standard medium containing supra-physiological (2.3 microM) folate concentration, display different levels of reactivity with the anti-folate-binding-protein (FBP) monoclonal antibody MOv18, which recognizes the alpha-isoform of the protein. Gel-filtration and absorption experiments indicated that on IGROVI cells this molecule accounts for all folic-acid binding at nanomolar concentrations. The aim of the study was to investigate the effect of extracellular folate levels on cells adapted to grow in medium containing physiological folate concentration (20 nM). By the ternary complex assay, all cell lines showed a marked depletion of intracellular reduced folates, compared with those in standard folate medium. The monitoring of FBP by MOv18 showed on IGROVI cells a transient up-regulation of the protein, whereas on the other cell lines, except SKOV3, no changes were detected. These data suggest that in these cells further over-expression of the molecule cannot generally be induced by lowering the extracellular folate concentration. On SKOV3, Scatchard analysis of 125I-MOv18 binding, as well as the evaluation of total folate binding capacity, showed a 2- to 3-fold stable increase of FBP expression after long-term growth in low-folate medium. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated in these cells a 1.5-fold increase in alpha-FBP mRNA. SKOV3 cells, maintained in vitro in medium containing supraphysiological and physiological (i.e., low-folate) concentrations were injected into nude mice. Weight differences, though not statistically significant, were observed in favour of low-folate-derived tumors. Immunohistochemical and immunochemical analysis of the tumor samples showed that in SKOV3 cells the receptor modulation can also be induced by restoring the physiological folate concentration in vivo.
Int J Cancer 1995 Nov 03
PMID:Growth of ovarian-carcinoma cell lines at physiological folate concentration: effect on folate-binding protein expression in vitro and in vivo. 759 Dec 38

Mutations in the human XPD gene result in a defect in nucleotide excision repair of ultraviolet damaged DNA and cause the cancer-prone syndrome xeroderma pigmentosum (XP). Besides XP, mutations in XPD can cause another seemingly unrelated syndrome, trichothiodystrophy (TTD), characterized by sulfur-deficient brittle hair, ichthyosis, and physical and mental retardation. To ascertain the underlying defect responsible for TTD, we have expressed the TTD mutant proteins in the yeast Saccharomyces cerevisiae and determined if these mutations can rescue the inviability of a rad3 null mutation. RAD3, the S. cerevisiae counterpart of XPD, is required for nucleotide excision repair and also has an essential role in RNA polymerase II transcription. Expression of the wild type XPD protein or the XPD Arg-48 protein carrying a mutation in the DNA helicase domain restores viability to the rad3 null mutation. Interestingly, the XPD variants containing TTD mutations fail to complement the lethality of the rad3 null mutation, strongly suggesting that TTD mutations impair the ability of XPD protein to function normally in RNA polymerase II transcription. From our studies, we conclude that XPD DNA helicase activity is not essential for transcription and infer that TTD mutations in XPD result in a defect in transcription.
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PMID:Lethality in yeast of trichothiodystrophy (TTD) mutations in the human xeroderma pigmentosum group D gene. Implications for transcriptional defect in TTD. 762 61

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.
Cancer Lett 1995 Aug 01
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

Potential mechanisms by which transforming growth factor beta 1 (TGF beta 1) inhibits cell growth include suppression of transcription of genes required for proliferation and inactivation of enzymatic activities that regulate progression through G1. To clarify which events are important for TGF beta 1 signaling, we have defined more precisely the times in G1 when the mouse keratinocyte cell line BALB/MK is sensitive to TGF beta 1-induced inhibition. TGF beta 1 is capable of inhibiting BALB/MK cell growth when the inhibitory factor is added to cells at any point before the G1-S transition. Synchronization at the G1-S boundary with mimosine, an inhibitor of initiation of origins of DNA replication, followed by release into S phase in the presence of TGF beta 1, indicated that cells lose sensitivity to TGF beta 1 as they enter the replicative phase. It is interesting that TGF beta 1 can inhibit BALB/MK cell growth late in G1, at a time when cell cycle progression is not blocked by an inhibitor of RNA polymerase II-mediated transcription. 5,6-dichlorobenzimidazole riboside (DRB). In addition, the ability of TGF beta 1 to inhibit entry into S phase in late G1 is unaffected by concurrent treatment with DRB. The data suggest that, at least when added to cultures that are in the latter few hours of G1, TGF beta 1 can inhibit cell cycle progression through mechanisms that do not involve stimulation or inhibition of gene expression at the transcriptional level.
Cancer Res 1995 Sep 01
PMID:Transforming growth factor beta 1 inhibits mouse keratinocytes late in G1 independent of effects on gene transcription. 764 Dec 12


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