Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Promiscuous transcriptional activity of the reticuloendotheliosis virus (REV) long terminal repeat (LTR) was detected in transient expression assays using LTR-chloramphenicol acetyltransferase-encoding gene chimeras, and cells of diverse species and tissue type; levels of expression from two different REV LTRs correlate with reports of pathogenicity of the respective viruses in vivo. REVs do not encode a transactivator targeted to the viral LTR, and cells infected with Marek's disease virus, a herpesvirus with an overlapping host range, do not express factors that preferentially enhance expression from REV or avian sarcoma/leukemia virus LTRs. REV LTRs work efficiently in human lymphoid cells, and are viable alternatives to promoters commonly used for expression of cloned genes. They may also prove useful in the identification of new, ubiquitous cellular transcription factors.
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PMID:Reticuloendotheliosis virus long terminal repeat elements are efficient promoters in cells of various species and tissue origin, including human lymphoid cells. 133 12

A possible approach to control of bovine lymphoproliferative disease caused by bovine leukaemia virus (BLV) may be the development of an "antiviral information immunity" based on the effect of anti-sense RNA (asRNA). A numbers of constructs were obtained, under control of various promotors (herpesvirus thymidine kinase, T-antigen SV40 promoter), carrying as DNA against gene X, the expression product of which is a transactivator of viral transcription from the BLV LTR promotor. As a model system for the analysis of antiviral activity of constructs developed, cloned continuous cell lines of BLV-producing FLK cells were used. The level of BLV expression in cells transfected with the constructs was determined by various parameters. Differences were detected in different clones obtained from non-transfected cells, as well as variation between transfected clones, as measured by reverse transcriptase, competitive radio-immunoassay for BLV p24, the viral particle count on agar membrane, and the tumorigenicity for nude mice. The differences in inhibition of expression of BLV genes and their products may be explained in terms of the site of integration of asDNA and the number of integrated copies.
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PMID:An investigation of the effect of antisense RNA gene on bovine leukaemia virus reproduction in cell culture. 133 48

Sixteen human T-cell lines were studied for the expression of a cell-adhesion molecule ICAM-1 and its counter-receptor LFA-1. The cell lines included 3 human T-cell-leukemia-virus-type-I (HTLV-1)-negative cell lines derived from acute lymphoblastic leukemia (ALL) and 13 HTLV-1-positive cell lines, 7 of them established from cord- or peripheral-blood T cells by in vitro transformation with HTLV-1, 2 derived from HTLV-1 carriers, and 4 derived from patients with adult T-cell leukemia (ATL). In sharp contrast to a basal level of ICAM-1 in 3 HTLV-1-negative ALL cell lines, strong induction of ICAM-1 was seen in all HTLV-1-positive T-cell lines except for MT-1, one of the 4 ATL cell lines used in the present study. On the other hand, the expression of LFA-1 (CD11a and CD18) was more or less similar among the cell lines with and without HTLV-1. Interestingly, however, 3 out of 4 ATL cell lines (TL-Om1, H582, HUT102) revealed striking depression of LFA-1 expression. Several lines of evidence strongly argued against direct involvement of the viral transactivator p40tax or some autocrine cytokines in the induction of ICAM-1 in HTLV-1-positive T-cell lines. It was also found that ICAM-1 and LFA-1 were involved in syncytium formation induced in the co-culture of HTLV-1-positive and HTLV-1-negative human T-cell lines. Implications of constitutive expression of ICAM-1 for certain clinical manifestations of ATL and of depression of either ICAM-1 or LFA-1 during progression of ATL are discussed.
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PMID:Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived cell lines. 135 35

Oxygen radical scavengers, such as dithiocarbamates and cysteine derivatives, inhibit activation of the ubiquitous transcription factor nuclear factor kappa B (NF-kappa B) after treatment of cells with tumor necrosis factor, phorbol ester, and interleukin-1. An involvement of oxygen radicals was more directly evident from the induction of NF-kappa B by low concentrations of H2O2 and the demonstration that cells stimulated with various NF-kappa B inducers release H2O2 and superoxide. In this study, we used the antioxidant pyrrolidine dithiocarbamate (PDTC) to investigate whether the activation of NF-kappa B by the viral transactivator Tax from human T-cell leukemia virus type I also depends on the production of reactive oxygen intermediates. The Tax-induced activation of the DNA-binding activity of NF-kappa B in Jurkat T cells was potently suppressed by micromolar concentrations of PDTC. Within the same concentration range, PDTC and two other dithiocarbamates also strongly interfered with transactivation of the long terminal repeat (LTR) of human immunodeficiency virus type 1 by Tax but had no effect on transactivation of the same LTR by Tat. Transactivation of the human T-cell leukemia virus type I LTR by Tax was also barely influenced. Tax seems to activate NF-kappa B by a mechanism shared with all other inducers of NF-kappa B tested so far. It appears that one of the pleiotropic activities of Tax leads to an enhanced production of oxygen radicals that are required for activation of NF-kappa B.
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PMID:Antioxidants selectively suppress activation of NF-kappa B by human T-cell leukemia virus type I Tax protein. 140 92

To study the signal transduction pathway leading to phorbol 12-myristate 13-acetate (PMA)-induced differentiation in human promyelocytic HL-60 leukemia cells, we examined the expression of protein kinase C (PKC) isozyme genes in HL-60 cells that are susceptible or resistant to PMA-induced differentiation. The PKC-alpha, -beta, -gamma, -delta, epsilon, and -zeta transcript levels were assessed by Northern blotting, and the PKC-alpha, -beta, and -gamma protein levels were examined by immunoblotting. The PMA-resistant cell variants HL-525 and HL-534 were found to be deficient in the PKC-beta isozyme RNA and protein as compared with the PMA-susceptible HL-60 and HL-205 cell lines. In addition, a "delta-like" PKC RNA species identified in these cells demonstrated a reduced abundance in the HL-525 and HL-534 cells. Southern blot analysis indicated that the observed reduction in PKC-beta gene expression does not appear to be due to a gross deletion or rearrangement of the gene. The expression of the early response genes junB, c-fos, and c-jun was attenuated in PMA-treated HL-525 and HL-534 cells as compared to the PMA-treated HL-60 and HL-205 cells. These results suggest that the signal transduction pathway that leads to PMA-induced differentiation in the HL-60 cell system requires PKC-beta and/or delta-like PKC for the proper expression of the early response genes, and ultimately the expression of genes that define the mature state.
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PMID:Protein kinase C beta gene expression is associated with susceptibility of human promyelocytic leukemia cells to phorbol ester-induced differentiation. 144 3

Chemically induced differentiation of Friend murine erythroleukemia cells (F-MELC) is a multistep process with a latent period of about 12 h preceding irreversible commitment to terminal maturation. To gain understanding of the early genetic response of F-MELC to the dimethyl sulfoxide (DMSO) inducer of F-MELC differentiation, we have investigated by Northern blot analysis the expression of fos and jun family genes that encode components of the transcription factor AP-1 complex. Our results show that c-jun mRNA is not detected at any time in untreated and DMSO-treated F-MELC. In contrast, DMSO-induced differentiation of F-MELC is associated with an early and transient induction of c-fos and junB mRNAs by 2 to 8 h treatment while in presence of dexamethasone, an inhibitor of F-MELC commitment, c-fos mRNA is not detected and junB mRNA remains at basal levels. junD mRNA is detected at low levels in untreated F-MELC and remains unchanged during DMSO treatment. Furthermore, DMSO treatment in a F-MELC cell line resistant to DMSO-differentiation does not result in an early induction of c-fos and junB mRNAs. Taken together, these results indicate that the DMSO-induced F-MELC differentiation is accompanied by an early co-induction of c-fos and junB during the latent period preceding the commitment to erythroid maturation.
Leukemia 1992 Sep
PMID:Co-induction of c-fos and junB during the latent period preceding commitment of Friend erythroleukemia cells to differentiation. 151 4

We examined the regulatory mechanisms of binding and transcriptional enhancement of the 21-bp core element of the enhancer of human T-cell leukemia virus type I (HTLV-I) in response to forskolin, 12-O-tetradecanoylphorbol-13-acetate (TPA), and a viral transactivator, p40tax. The 21-bp core element has been shown to bind to a cyclic AMP-responsive element binding protein (CREB)-like molecule at the site of an imperfect palindrome containing the TGAC motif. Experiments with oligonucleotides with mutations in the imperfect palindrome demonstrated that one TGAC motif is necessary and sufficient for both the binding of the CREB-related factor and transcriptional activity in response to forskolin in a human T-cell line, Jurkat. We also found that binding of the CREB-like factor to the 21-bp core element was enhanced by treatment with TPA, with little effect on transcriptional activity; in contrast, forskolin and p40tax did not facilitate binding, though they enhanced transcription. The combination of forskolin and TPA synergistically induced the transcription activity of the element, showing a hierarchical mechanism of regulation of the HTLV-I core enhancer element to levels sufficient for formation of the factor-enhancer complex and for activation of the complex. Added to those findings, our results indicate that the modes of activation by forskolin and p40tax are different from each other.
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PMID:Multistep regulation of enhancer activity of the 21-base-pair element of human T-cell leukemia virus type I. 153 52

The tax protein of human T-cell leukemia virus type I (HTLV-I) is known to be a potent transactivator of its own long terminal repeat (LTR) promoter and the cellular genes (IL-2, IL-2R, c-fos and GM-CSF). These effects of tax have been studied in vitro, mostly in T-cell lines. To determine its function in vivo in multiple cell types, we have used two transgenic mouse lines in which tax is expressed under the control of the LTR (LTRtax) or murine Thyl. 2 (Thytax) transcriptional regulatory sequences. Tax protein is expressed in fibroblasts, salivary gland, skeletal muscle, bone matrix and thymus tissue. In these tissues the expression of endogenous IL-2R, c-fos, GM-CSF, Zif268, IL-6, and PDGF-B were studied. In fibroblastic tumors GM-CSF, IL-6, PDGF-B, Zif268, c-fos were expressed at high levels. No significant changes in expression of these genes were seen in other tissues. This suggests that tax mediated transcriptional transactivation alone is not sufficient to cause accumulation of these cellular gene products. Other events which occur during tax mediated transformation in vivo allow high levels of cellular gene expression constitutively.
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PMID:[HTLV-I tax mediated activation of cellular genes in transgenic mice]. 191 30

Short-term stimulation (up to 16 hours) of interleukin-3 (IL-3)-dependent mouse bone marrow-derived mast cells, Abelson transformed mouse liver-derived mast cells, or rat basophilic leukemia cells by either IgE-Ag or calcium ionophore A23187 resulted in inhibition of their proliferation as measured by 3H-thymidine incorporation and MTT (tetrazolium) assays, and in accumulation of the mRNAs of c-fos, c-jun, junB and slightly of junD proto-oncogenes. The involvement of protein kinase C (PKC) in these responses was investigated by using several approaches of enzyme activity regulation. Direct activation of the PKC was achieved by short-term exposure of the cells to the PKC-specific activator phorbol 12-myristate-13-acetate (PMA). Inhibition of PKC activity was obtained by either prolonged treatment of the cells with PMA or by exposure of the cells to the PKC inhibitors H-7 and staurosporine. The results showed the following: (1) Short-term exposure of mast cells to PMA was sufficient to induce inhibition of proliferation. (2) An increase in PKC activity was associated with a decrease in the proliferation of IgE-dinitrophenol (DNP) or calcium ionophore A23187-stimulated cells. (3) A direct correlation was found between the increase in PKC activity and the increase in the level of the mRNAs of the jun proto-oncogenes in cells activated by both stimuli mentioned. (4) While an increase in PKC activity was associated with the upregulation of the level of c-fos mRNA during calcium ionophore A23187 stimulation, it showed the opposite effect on the expression of the mRNA of this proto-oncogene when the cells were triggered by IgE-DNP. Therefore, we concluded that PKC plays various roles in the expression of the mRNA of c-fos in activated mast cells depending on the stimulus involved. In addition, the expression of the mRNA of c-jun and junB proto-onogenes is not coordinately regulated with that of c-fos during immunologic stimulation. This discordancy, which is associated with the increase in PKC activity in mast cells, may play a role in the regulation of the transcription of AP-1-responsive genes, and therefore could be associated with the regulation of proliferation of these cells.
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PMID:Protein kinase C regulates proliferation of mast cells and the expression of the mRNAs of fos and jun proto-oncogenes during activation by IgE-Ag or calcium ionophore A23187. 193 49

Human T-lymphotropic viruses (HTLV-I and -II) and bovine leukaemia virus (BLV) express transactivator proteins able to increase long terminal repeat (LTR) directed viral expression. These transacting factors are though to be involved in the induction of leukaemia by these viruses. Transfection of BLV transactivator p34tax together with Ha-ras immortalizes and transforms rat embryo fibroblasts, in vitro. The transformed cell induce tumours in nude mice. These data emphasize the causal role exerted by p34tax in in vivo tumorigenesis.
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PMID:Cooperation between bovine leukaemia virus transactivator protein and Ha-ras oncogene product in cellular transformation. 215 45


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