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)

We established an in vitro system representing BL-type EBV infection, which is characterized by expression of EBNA1, EBER, BARF0, and LMP2A, and absence of EBNA2 and LMP1 expression (Shimizu et al. 1994; Komano et al. 1998). Comparison of EBV-positive and -negative Akata cell clones revealed that EBV contributes to the malignant phenotype and resistance to apoptosis. This is clear evidence that EBV is not a passenger and plays a role in BL. Moreover, we found that EBERs are responsible for these phenotypes (Komano et al. 1999). In the transfection study, EBER-expressing Akata cell clones restored the malignant phenotype, resistance to apoptosis and upregulated expression of bcl-2 protein to a level comparable to the restoration rate of EBER expression compared with EBV-reinfected cell clones. Many RNAs are known to have catalytic functions; however, there has been no report describing an oncogenic RNA. This is the first paper that provides evidence that RNA polymerase III-transcribed virus-encoded small RNAs affect the malignant phenotype and resistance to apoptosis. Like Akata cells (Takada et al. 1991), all the BL cells possess a chromosomal translocation involving the c-myc locus, which results in constitutive activation of the c-myc gene (Klein 1981). In mammalian cells, deregulated expression of c-myc has been shown to contribute not only to tumorigenesis (Land et al. 1983) but also to induce apoptosis (Askew et al. 1991; Evan et al. 1992; Milner et al. 1993). Therefore, BL cells are predisposed to c-myc-induced apoptosis. Our data imply that EBV infection would upregulate expression of bcl-2 protein to protect cells from c-myc-induced apoptosis, and to allow c-myc to exert its oncogenic functions (Vaux et al. 1988; Brito-Babapulle et al. 1991; Bissonnette et al. 1992; Fanidi et al. 1992; Karsan et al. 1993; Mohammad et al. 1993; Oltvai et al. 1993; Marin et al. 1995). In this way bcl-2 might cooperate with c-myc in the development of BL (Fig. 5).
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PMID:Role of Epstein-Barr virus in Burkitt's lymphoma. 1144 59

Benign mesenchymal neoplasms associated with rearrangements of the DNA architectural factor gene HMGIC on chromosome 12 include lipomas, uterine leiomyomata, pulmonary chondroid hamartomas, endometrial polyps, salivary gland pleomorphic adenomas, and breast fibroadenomas. Although HMGIC also has been implicated in the pathobiology of aggressive angiomyxoma of the vulva, the molecular mechanisms pertaining to this neoplasm are unclear. Tissue from a recurrent aggressive angiomyxoma was investigated by cytogenetic and expression analysis for HMGIC and HMGIY. The trypsin-Giemsa-banded karyotype showed a clonal translocation between chromosomes 8 and 12 [46,XX,t(8;12)(p12;q15)]. Fluorescence in situ hybridization (FISH) analysis with whole chromosome paint probes for chromosomes 8 and 12 excluded cryptic involvement of other chromosomes. The chromosome 12 breakpoint was mapped with two-color FISH analysis using cosmid probes at the 5' and 3' termini of HMGIC. Both cosmid probes showed hybridization to the normal chromosome 12 and the der(12) chromosome, indicating that the breakpoint was 3' (telomeric) to the gene. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed HMGIC expression in the tumor, and immunohistochemistry localized HMGIC expression to the tumor's spindle cells. Like numerous benign mesenchymal tumors, this locally aggressive tumor is associated with rearrangements near or within HMGIC, but chimeric gene formation was not required for tumorigenesis. Inappropriate expression of this DNA binding protein, however, may be important in the pathobiology of this tumor. Understanding the pathogenetic mechanism may also be helpful in developing new diagnostic tools for identifying residual disease.
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PMID:Chromosomal translocation t(8;12) induces aberrant HMGIC expression in aggressive angiomyxoma of the vulva. 1155 Feb 85

Tumor-associated chromosomal translocations lead to the formation of chimeric fusions between the EWS gene and one of five different ETS transcription factors in Ewing's family tumors (EFTs). The resultant EWS/ETS proteins promote oncogenesis in a dominant fashion in model systems and are necessary for continued growth of EFT cell lines. EWS belongs to a family of genes that encode proteins that may serve as adapters between the RNA polymerase II complex and RNA splicing factors. EWS/ETS fusions have biochemical characteristics of aberrant transcription factors and appear to promote abnormal cellular growth by transcriptionally modulating a network of target genes. Early evidence suggests that EWS/ETS proteins may also impact gene expression through alteration in RNA processing. Elucidation of EWS/ETS target gene networks in the context of other signaling pathways will hopefully lead to biology based therapeutic strategies for EFT.
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PMID:Biology of EWS/ETS fusions in Ewing's family tumors. 1160 24

Hepatitis B virus (HBV) gene expression is mainly regulated at the transcription initiation level. The viral X protein (pX) is a transcription coactivator/mediator targeting TFIIB for the recruitment of RNA polymerase II. Here we report a novel pX nuclear target designated HBXAP (hepatitis B virus X-associated protein). HBXAP is a novel cellular nuclear protein containing a PHD (plant homology domain) finger, a domain shared by many proteins that play roles in chromatin remodeling, transcription coactivation, and oncogenesis. pX physically interacts with HBXAP in vitro and in vivo via the HBXAP region containing the PHD finger. At the functional level HBXAP increases HBV transcription in a pX-dependent manner suggesting a role for this interaction in the virus life cycle. Interestingly, HBXAP collaborates with pX in coactivating the transcriptional activator NF-kappaB. Coactivation of NF-kappaB was also observed in tumor necrosis factor alpha-treated cells suggesting that pX-HBXAP functional collaboration localized downstream to the NF-kappaB nuclear import. Collectively our data suggest that pX recruits and potentiates a novel putative transcription coactivator to regulate NF-kappaB. The implication of pX-HBXAP interaction in the development of hepatocellular carcinoma is discussed.
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PMID:Hepatitis B virus pX interacts with HBXAP, a PHD finger protein to coactivate transcription. 1178 98

The bcl-x gene product has two forms, bcl-xl and bcl-xs. The bcl-xl form, similar to bcl-2, inhibits apoptosis. Reverse transcriptase-polymerase chain reaction/single-stranded conformation polymorphism (RT-PCR-SSCP) gel analysis was used to screen for mutations of the bcl-xl transcript of 50 non-Hodgkin's lymphoma (NHL) cases. One missense mutation in a patient with diffuse large B-cell lymphoma was found. Sequence analysis of this case showed that AGC (Ser) was mutated to GGC (Gly) in codon 154. An examination of mutation and/or polymorphism in born marrow samples of this case and 50 normal controls by the RT-PCR-SSCP method could not detect bandshifts. Mutation of the bcl-x gene in NHL has not been reported previously. There is a possibility that mutation of the bcl-x gene play a role in the tumorigenesis of NHL.
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PMID:Mutation of bcl-x gene in non-Hodgkin's lymphoma. 1183 37

The Atlas human cDNA expression array was used to evaluate gene expression profile changes in the genesis of human lung adenocarcinomas and squamous cell carcinomas. Gene expression changes between adenocarcinomas and squamous cell carcinomas were also analyzed. Of the 588 gene targets, 262 genes were expressed in these tissues and, of these, 45 genes were differentially expressed by at least two-fold in tumor tissues compared to corresponding normal tissues. Semiquantitative reverse-transcriptase polymerase chain reaction was used to confirm gene expression changes. Only those genes that reflected changes in >50% of the analyzed tissues were included in the final analysis. Ultimately, 26 genes were evaluated with 14 genes overexpressed and 12 genes underexpressed compared to matching normal lung tissues. Although similar expression changes were detected in adenocarcinomas and squamous cell carcinomas for most of the genes analyzed, some subtype-specific differences were also found. Genes encoding cell cycle regulators, intracellular signal transducers, cell receptor and adhesion molecules, growth factors, oncogenes, and apoptotic effectors were differentially expressed in this study. These gene expression changes may directly contribute to the initiation or progression of human lung cancer or may be secondary effects of the tumorigenesis process. Regardless, many of these differences may be useful in the diagnosis and/or treatment of this deadly disease.
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PMID:Differential expression of critical cellular genes in human lung adenocarcinomas and squamous cell carcinomas in comparison to normal lung tissues. 1189 69

GG-62 is a cell line previously thought to be derived from an atypical Ewing tumor (ET). Reverse-transcriptase polymerase chain reaction revealed an in-frame fusion between the Ewing sarcoma gene ( EWS) codon 325 and the activating transcription factor 1 gene ( ATF1) codon 65 which permits the production of chimeric EWS-ATF1 oncoproteins. We also identified the genomic breakpoint resulting from a reciprocal t(12;22)(q13;q12), which is the hallmark of malignant melanoma of soft parts (MMSP). We applied Affymetrix human cancer G110 arrays to compare the gene expression patterns of GG-62 and other cell lines derived from small blue round cell tumors of childhood. Hierarchical clustering of 463 differentially expressed genes distinguished GG-62 from the ETs, as well as the neuroblastomas, and revealed a cluster of 36 upregulated genes. Several of these genes are involved in signal transduction pathways that may be critical for maintaining cell transformation; some examples are avian erythroblastic leukemia viral oncogene homolog 3 ( ERBB3), neuregulin 1 ( NRG1), fibroblast growth factor 9 ( FGF9), and fibroblast growth factor receptor-1 ( FGFR1). Furthermore, genes near the chromosome-12q13 breakpoint exhibited increased expression of GG-62 including ERBB3, NR4A1 (nuclear receptor subfamily 4, group A, member 1), cyclin-dependent kinase 2 ( CDK2), and alpha 5 integrin ( ITGA5). Altogether our findings demonstrate the MMSP derivation of GG-62 and may shed light on the mechanisms of tumorigenesis in this rare disease.
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PMID:Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays. 1202 21

Only a small number of human synovial sarcoma cell lines have been reported, and of those, not all have been fully characterized, especially at the molecular level. We describe here the establishment and characterization of a new human cell line, FU-SY-1, which originated from a monophasic fibrous synovial sarcoma arising in the supinator muscle of a 31-year-old woman. This cell line propagated continuously in vitro for 73 serial passages for more than 36 months. FU-SY-1 cells in vitro were rather small, exhibited a spindle or polygonal shape without conspicuous pleomorphism, and expressed c-Met and hepatocyte growth factor (HGF) as determined by immunocytochemistry. Cytogenetically, FU-SY-1 cells maintained a consistent karyotype: 47, X, +7, t(X;18)(p11.2;q11.2), the same as that of the original tumor specimen. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated a SYT-SSX fusion transcript and expression of c-Met and HGF mRNA in FU-SY-1 cells. A subsequent sequence analysis using the PCR products confirmed that the detected messages were derived from the SYT-SSX1 fusion gene. This cell line, FU-SY-1, established from a monophasic fibrous synovial sarcoma, may therefore be a useful tool for investigation of the mechanisms of tumorigenesis and progression in human synovial sarcomas.
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PMID:Establishment of a new human synovial sarcoma cell line, FU-SY-1, that expresses c-Met receptor and its ligand hepatocyte growth factor. 1206 44

Nucleotide excision repair provides an important cellular defense against a large variety of structurally unrelated DNA alterations. Most of these alterations, if unrepaired, may contribute to mutagenesis, oncogenesis, and developmental abnormalities, as well as cellular lethality. There are two subpathways of nucleotide excision repair; global genomic repair (GGR) and transcription coupled repair (TCR), that is selective for the transcribed DNA strand in expressed genes. Some of the proteins involved in the recognition of DNA damage (including RNA polymerase) are also responsive to natural variations in the secondary structural features of DNA. Gratuitous repair events in undamaged DNA might then contribute to genomic instability. However, damage recognition enzymes for GGR are normally maintained at very low levels unless the cells are genomically stressed. GGR is controlled through the SOS stress response in E. coli and through the activated p53 tumor suppressor in human cells. These inducible responses in human cells are important, as they have been shown to operate upon chemical carcinogen DNA damage at levels to which humans are environmentally exposed. Interestingly, most rodent tissues are deficient in the p53-dependent GGR pathway. Since rodents are used as surrogates for environmental cancer risk assessment, it is essential that we understand how they differ from humans with respect to DNA repair and oncogenic responses to environmental genotoxins. In the case of terminally differentiated mammalian cells, a new paradigm has appeared in which GGR is attenuated but both strands of expressed genes are repaired efficiently.
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PMID:Subpathways of nucleotide excision repair and their regulation. 1248 11

Transcription in eukaryotic cells requires the remodeling of chromatin and the assembly of functional preinitiation complexes (PICs), which contain the general transcription factors (GTFs), RNA polymerase II (Pol II), and coactivators. Genetic and biochemical studies have implicated the multisubunit Mediator coactivator complex (Med) as a critical component of the PIC, a direct target of activators, and a checkpoint for regulated gene expression during differentiation, development (reviewed in ), signaling, and oncogenesis. In this report, we show that a complex containing the activator GAL4-VP16, Med, and TFIID/TFIIA (DA) recruits pol II and the remaining GTFs to a model promoter in vitro. A preassembled DAMed complex bypasses the requirement for an activator. We also demonstrate that coordinated assembly of DAMed is essential to establishing a functional PIC. We conclude that the DAMed complex generates a platform that supports activated levels of PIC assembly and transcription.
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PMID:Assembly of a mediator/TFIID/TFIIA complex bypasses the need for an activator. 1272 37


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