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)

Previously we reported the isolation of a factor, named the R-protein, which strongly repressed RNA polymerase II [EC 2.7.7.6] of Ehrlich ascites tumor cells. In the present work this factor was found to contain much RNA (ratio of RNA to protein, 2.3 to 1). The RNA was G:C rich, with a very high content of guanylic acid (about 38%). On equilibrium density gradient centrifugation in Cs2SO4 solution, the RNA became distributed above free RNA, but after digestion of the R-protein with pronase the RNA cosedimented with free RNA. Thus the R-protein is a complex of RNA and protein.
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PMID:DNA dependent RNA polymerase from Ehrlich ascites tumor cells. V. Characterization of a factor repressing RNA polymerase II as a ribonucleoprotein. 122 7

The synthesis of potentially specific antitumor peptide derivatives of daunorubicin is presented. The interaction specificites of the drugs with nucleic acids have been examined via stop-flow kinetics as well as the inhibition of DNA template activity. It is found that the biological activity of the daunorubicin derivatives against the mouse P388 tumor is directly proportional to RNA polymerase inhibition and inversely proportional to the rate of dissociation of the DNA complex. It is concluded that the biological efficacy of drugs which act at the replicative and transcriptional level may be estimated by the more rapid in vitro techniques provided that problems of permeability, solubility, stability, etc., in vivo are not encountered.
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PMID:Sturcture-activity relationship of daunorubicin and its peptide derivatives. 125 61

We have analysed the splicing patterns of human papillomavirus (HPV) type-16 mRNAs in a human epithelial cell line immortalized by HPV 16 (HPKII), in cell lines established from cervical carcinomas (SiHa and CaSki) and in pre-invasive and invasive carcinomas of the cervix. The presence of mRNA species previously described, which could encode the E6, E6I, E6II, E6III, E7, E2, E2C, E4, E5 and L1 proteins, was determined, using the RNA polymerase chain reaction (PCR) technique with primers that flank unique splice sites. The state of the viral DNA in the tumor biopsies was established by Southern blot analysis. The various HPV 16 transcripts could be detected in cell lines and in tumor biopsies. The size of the RNA PCR products were in agreement with the previously mapped splice sites. The full range of transcripts was revealed in the HPKII cell line and in a number of pre-invasive carcinomas. Messenger RNAs which could encode the E6III, E4 and E5 proteins were most prevalent in all types of tumor. The overall results of DNA and RNA analyses in cell lines and tumor specimens indicate that (1) expression of either of the early or late transcripts studied is not specifically related to (a) tumor stage or (b) the physical state of the viral genome; and (2) alterations in the splicing patterns of HPV 16 transcripts may not be involved in tumor progression.
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PMID:Expression and splicing patterns of human papillomavirus type-16 mRNAs in pre-cancerous lesions and carcinomas of the cervix, in human keratinocytes immortalized by HPV 16, and in cell lines established from cervical cancers. 131 Apr 88

Carcinogen-induced expression of the integrated viral genome was examined on SV40-transformed Chinese hamster cells. Carcinogen treatment markedly increased the transcription rate and the steady state mRNA level of both early and late viral transcripts. Carcinogen-induced transcription was mediated by RNA polymerase II. The increase in viral gene expression was also detected at the protein level, although at a reduced amplitude. Enhanced transcription was apparent as early as 12 hr postexposure and was considerably elevated after 24-36 hr. The increased gene expression depended on the existence of a functional replication machinery, as indicated by two lines of evidence. First, a cell line that harbors origin-deleted SV40 failed to respond to carcinogen treatment by increasing transcription and expression of T antigen. Furthermore, carcinogen-induced overtranscription was inhibited by aphidicolin, an inhibitor of DNA polymerase alpha. The involvement of the replication apparatus in the enhanced expression points to mechanistic similarities between the carcinogen-induced viral gene expression in the drug-treated semipermissive cells and the SV40 lytic pathway under permissive conditions. It is therefore suggested that cellular permissivity to viral development is enhanced following exposure to carcinogens. The implications of these findings for the nature of cellular permissivity to viral infection and the synergistic effects of carcinogens and tumor viruses are discussed.
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PMID:Carcinogen-induced activation of SV40 gene expression in a semi-permissive environment. 132 84

Tumor biopsies from exophytic and flat condylomas at different locations on the genital epithelium (10 cases) and in cervical intraepithelial neoplasia (CIN) grades 1-2 (6 cases) were analysed for HPV types 6 and 11 DNA and RNA. The presence of mRNA species which could encode the E6, E7, E1M, E2, E2C, E4, E5 and L1 proteins was determined using the RNA polymerase chain reaction (PCR) technique with primers that flank previously mapped or predicted splice sites. The state of the viral DNA in the tumor biopsies was established by Southern blot analysis. We could detect the various mRNA species in biopsies from condylomas associated with both HPV types. The size of the RNA PCR products were in agreement with the previously mapped splice sites of mRNAs recovered from an experimental condyloma induced by HPV11. The major viral transcript encoding the E1i--E4 protein was detected in all the tumor biopsies. From the rare transcripts the rate of detection of mRNA species encoding the E1M, E2C proteins was the highest. In 2 of 6 CIN biopsies analysed only the major viral transcript was detected. The overall results of this study suggest that early gene products of HPV types 6 and 11 may be important in the induction of cellular proliferation and condylamatous differentiation but these possibly may not be required for the development of the HPV-associated cervical neoplasia.
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PMID:Differential expression of HPV types 6 and 11 in condylomas and cervical preneoplastic lesions. 132 75

The rearranged region of the tre oncogene originating from chromosomes 5q23q31 and 18q12 was cloned from tumor genomic DNA, sequenced and aligned with wild-type sequences cloned from a normal human genomic library. In the breakpoint region each wild-type sequence contained two Alu repeats. The recombination occurred between the 3'-most Alu from chromosome 5 and the 5'-most Alu from chromosome 18 and, consequently, resulted in a hybrid Alu flanked with one Alu on either side. The recombinant joint was located to a 20-bp homology region in left arms of the Alu repeats involved in recombination. The same homology region was identified in the hybrid Alu of the rearranged tre. At its 5' extremity the homology region overlaps the B box of Alu-borne RNA polymerase III promoter. The 100% identity score in the region of homology suggests that the recombination process was conservative and not error prone.
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PMID:Rearrangement of the human tre oncogene by homologous recombination between Alu repeats of nucleotide sequences from two different chromosomes. 146 55

Eight cases of Philadelphia positive acute leukemia (Ph+AL) were compared with 13 cases of Ph+ chronic myelogenous leukemia in blast crisis (BC) and 10 cases of Ph negative acute lymphoblastic leukemia (Ph-ALL) based on the clinical and molecular biological findings. Distinguishing clinical features were a high leukocyte count (median; 147.9 x 10(3)/microliters) for Ph+AL, and a high incidence of tumor formation and basophilia for BC. A cytogenetic study demonstrated the disappearance or marked reduction of Ph+ metaphases in Ph+AL in remission, while Ph+ cells persisted in BC. The major bcr gene was not rearranged in 4 Ph+AL cases, whereas it was found rearranged in 4 other cases of Ph+ AL and 6 cases of BC. Reverse transcriptase polymerase chain reaction technique demonstrated the presence of minor bcr/abl mRNA in the former three cases, and major bcr/abl mRNA in the latter 4 cases. Remission rates were 63% for Ph+AL, 38% for BC, and 100% for Ph-ALL, and the 50% survival were 12, 5 and 29 months, respectively. It was concluded that Ph+AL can be differentiated from BC by a marked reduction of Ph+ cells at remission, and that the prognosis of Ph+AL is better than BC, but worse than Ph-ALL.
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PMID:[Clinical and molecular biological study of Ph positive acute leukemia: comparison with blast crisis of chronic myelogenous leukemia and Ph negative acute lymphoblastic leukemia]. 163 16

This report describes a novel assay involving the polymerase chain reaction (PCR) and RNase protection for the rapid and sensitive detection of malignant lymphoid cells by nucleotide sequences within their individual rearranged gamma T-cell receptor (TCRG) genes. In this assay, clonal rearrangements are amplified from the DNA of diagnostic tumor specimens using a consensus V segment primer and a consensus J segment primer to which the promoter for T7 RNA polymerase has been appended. The PCR product from this amplification is transcribed into a radiolabeled RNA probe. Test RNA transcribed from the opposite DNA strand is synthesized by similar methods from TCRG genes of a subsequent biopsy specimen. The test RNA is hybridized with the probe, and mismatched nucleotide sequences in the RNA hybrids are digested by RNase A. Detection of fully protected probe by means of polyacrylamide gel electrophoresis and autoradiography indicates the presence of malignant cells in the test specimen. Dilution experiments with DNA of cell lines from acute lymphoblastic leukemias (ALLs) show that detection of one tumor cell among 10(5) normal bone marrow cells is usually possible. Residual disease was also successfully detected in several cases of ALL during clinical remission, including detection in one case at the 10(-5) level. The procedure described here may provide a simplified and rapid method for the sensitive diagnosis and monitoring of lymphoid malignancies. This procedure should be applicable to most antigen receptor genes, and unlike most comparable methods, requires neither analysis of nucleotide sequence nor synthesis of tumor-specific oligonucleotide probes or primers.
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PMID:Sensitive detection of clonal antigen receptor gene rearrangements for the diagnosis and monitoring of lymphoid neoplasms by a polymerase chain reaction-mediated ribonuclease protection assay. 165 9

The murine gene pro1 has been cloned from JB6 epidermal cell lines that are sensitive to neoplastic transformation by tumor promoters. Insensitive JB6 variants acquire susceptibility to neoplastic transformation by tumor promoters when transfected with pro1. The repetitive nature of pro1 was indicated by sequence and Southern analysis. In contrast, northern analysis of RNA from promotion-sensitive cells revealed the presence of a small pro1-hybridizing transcript. Strand-specific RNA probes implicated an RNA polymerase III (RNAPIII) coding domain in pro1 as the source of this hybridization signal. Ribonuclease protection of gel-purified pro1 RNA from JB6 variant cell lines identified a 130-nucleotide transcript. The size of this transcript is compatible with in vitro RNAPIII transcription of pro1. Deletion mapping of pro1 by exonuclease III demonstrated that the biologically active domain included the RNAPIII transcription unit. RNA probes map pro1 RNA within the activity domain. These results delineate an activity domain of 597 nucleotides and suggest that a small RNA is the product of promotion-sensitivity gene pro1.
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PMID:Deletion mapping of tumor promotion-susceptibility gene pro1 implicates an RNA polymerase III transcription unit. 169 83

The mechanism of tumor cell killing by HO-221, a novel benzoylphenylurea derivative that shows broad-spectrum antitumor activities, was studied. HO-221 strongly inhibited the activity of mammalian DNA polymerase alpha but not that of DNA polymerases beta or gamma. The inhibition was equivalent to that induced by aphidicolin and ara-CTP, which were selective inhibitors of the enzyme. Furthermore, the inhibition by HO-221 of DNA polymerase alpha was found to be non-competitive with respect to dCTP as a substrate, unlike that induced by aphidicolin and ara-CTP. The inhibition was reduced the addition of an excess of DNA polymerase alpha but not by excess amounts of activated DNA as a template primer. These results suggest that HO-221 inhibits the activity of DNA polymerase alpha by direct interaction with the enzyme in contrast to the impairment of template activity through intercalation into DNA induced by anthracycline compounds. On the other hand, HO-221 showed almost no effect on RNA polymerase activity, the reverse transcriptase activity of avian myeloblastosis virus or protein synthesis in a cell-free system. The flow-cytometry analysis revealed that HO-221 accumulated HL-60 cells in G1-S phases at a low concentration but increased the number of cells in the G1 phase at a higher concentration, stopping cell-cycle progression. The results suggest a correlation between cell-cycle progression and inhibition by HO-221 of DNA polymerase alpha, which plays a role in DNA replication during the S phase in living cells.
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PMID:Mechanism of tumor cell killing by HO-221, a novel antitumor compound. 170 66


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