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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of murine mammary tumor virus (MuMTV) production by mammotropic hormones, hormonomimetic substances, and cyclic nucleotides was investigated. The virus produced in control and treated mammary tumor cell cultures was quantitated by measuring the supernatant reverse transcriptase activity in exogenous reaction using poly(rC).oligo(dG) as template-primer. Two days after exposure, the synthetic glucocorticoid, dexamethasone (DXMT), increased spontaneous MuMTV production at optimal concentration (0.1 mumol) up to ten times. Dibutyryl derivative of cyclic AMP had no effect on spontaneous MuMTV production, whereas the drug potentiated suboptimal concentrations of the glucocorticoid. Natural prostaglandins, potent agonists of adenylate cyclase catalyzing intracellular synthesis of cyclic AMP, enhanced both basal (up to five times) and DXMT-stimulated (up to 1.6 times) MuMTV replication. The MuMTV-stimulating activity of prostaglandins decreased in the order of PGA1 greater than PGE1 greater than PGB1 greater than PGF2 alpha. Prostaglandins can be replaced partially by norepinephrine and isoproterenol by enhancing the DXMT-mediated MuMTV stimulation, whereas these drugs remained without effect on spontaneous MuMTV production. Theophylline, an antagonist of cAMP-phosphodiesterase converting cAMP to AMP, enhanced the virus-stimulating activity of DXMT as well as of prostaglandins. The enhancement of MuMTV production by adenylate cyclase agonists do not correlate absolutely with the estimates of intracellular cAMP levels, since the highest amounts of cAMP has been repeatedly observed in cells treated with PGE1 and norepinephrine. The results indicate that besides hormones, other hormone-like substances and cyclic nucleotides may be involved in the complex mechanism of hormone-regulated MuMTV genome expression.
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PMID:Role of natural prostaglandins in the control of murine mammary tumor virus expression. 628 Dec 84

Baboon endogenous virus (BaEV) is a type C retrovirus present in multiple proviral copies in the DNA of baboons. Although interspecies antigenic determinants present on reverse transcriptase and gag proteins are shared among all mammalian type C viruses, no nucleic acid homology between BaEV and other type C viruses (except RD-114) has been found in conventional liquid hybridization experiments. In this study, we used restriction fragments of cloned BaEV DNA immobilized on nitrocellulose to test for relatedness with [(32)P]cDNA's of various type C and type D viruses. We detected the following distant relationships previously found only through immunological and protein sequencing techniques: (i) eight type C viral cDNA's (the endogenous virus of rhesus monkeys, feline leukemia virus, simian sarcoma virus, gibbon ape leukemia virus, Rauscher murine leukemia virus, BALB-2, NZB, and RD-114) and two type D viral cDNA's (Mason-Pfizer monkey virus and squirrel monkey retrovirus) were able to hybridize with cloned BaEV DNA; (ii) the eight type C probes hybridized to restriction fragments spanning most of the BaEV genome, but only RD-114 hybridized to fragments within the 1.9 kilobases at the 3' end of the genome; (iii) the two type D probes hybridized primarily to fragments within the 1.9 kilobases at the 3' terminus and weakly or not at all elsewhere; and (iv) [(32)P]cDNA's of several other oncornaviruses (mouse mammary tumor virus, equine infectious anemia virus, bovine leukemia virus, and reticuloendotheliosis virus) exhibited no homology with BaEV DNA. DNA sequence analysis has allowed us to orient the BaEV restriction map with the genetic map at both ends of the genome. Homologies between retroviral cDNA's and BaEV clone restriction fragments could thus be related to specific BaEV genes. Whereas type C cDNA's hybridized to fragments from gag, pol, and the pol-env junction, squirrel monkey retrovirus cDNA hybridized only to a fragment coding for the p15E portion of env. Mason-Pfizer monkey virus cDNA also hybridized within the p15E region, but exhibited homology to the 3' half of gp70 as well. These results are discussed relative to previously reported antigenic relatedness of retroviral proteins. The data suggest that BaEV represents an important link in oncornavirus evolution.
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PMID:DNA sequence relationship of the baboon endogenous virus genome to the genomes of other type C and type D retroviruses. 628 72

Single-stranded complementary DNA (cDNA) of the RNA of Gazdar murine sarcoma virus, Gz-MSV/MuLV; Moloney murine leukemia virus, M-MuLV; mouse mammary tumor virus, MMTV; and simian sarcoma virus, SSV-1, were synthesized in endogenous reverse transcriptase reaction. Gz-MSV/MuLV cDNA was also synthesized in exogenous in vitro reverse transcriptase reactions. In the endogenous reaction, 30-35S, or 6.0- to 7.9-kilobase-length cDNA transcripts were synthesized in high yield. In comparison, transcripts synthesized in exogenous reactions were 6.7S, or 0.39 kilobases. The complementarity of the transcripts was verified by both RNA/DNA hybridization and protection studies. dG and dC sequences were detected in 50-77% of the cDNA molecules by affinity chromatography, by annealing and masking studies, and by resistance to S1 nuclease. dT and dA sequences were not detected in the transcripts. These findings are discussed in relation to the possible selective blocking of transcription of retrovirus genes without interfering significantly with the transcription of cellular genes.
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PMID:Complementary DNA copies of leukemia and sarcoma virus RNA contain sequences of deoxycytidylate and deoxyguanylate. 629 64

Clonal derivatives 8 and 11 of the T47D human breast carcinoma cell line release particles that have the biochemical characteristics of a retrovirus. Particles recovered from cultures of [3H]uridine-labeled clone 11 had a density of 1.18 g/ml and contained 60-70S and 35S RNAs associated with reverse transcriptase activity. The production of these particles was steroid-dependent. Clone 8 particles had a higher density, 1.195 g/ml, and their production was independent of steroid hormone. By RIA, antigens crossreactive with the 52,000-dalton envelope glycoprotein gp52, the major external protein of mouse mammary tumor virus, were found associated with these particles and in the media. Most of the gp52-related antigen was in soluble form, but it was enriched in the particle preparation. A lesser amount of antigen was distributed within the cultured cells. Absorption of rabbit antibody to gp52 with clone 11 particle preparations eliminated the ability of this antibody to detect immunocytochemically a crossreactive antigen previously localized in tissue sections of human breast carcinoma. These results indicate that the particle isolates from T47D contain the same gp52-related antigen found in human breast carcinomas and constitute an excellent source for the purification and characterization of this antigen.
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PMID:Properties of retrovirus-like particles produced by a human breast carcinoma cell line: immunological relationship with mouse mammary tumor virus proteins. 633 Jul 48

Characterization of numerous independently derived cell lines is necessary in order to establish reliable biological criteria applicable to transformed mammary epithelial cells. A mammary tumor cell line (DMBA-2/BALB) and clonal derivatives have been established from an adenocarcinoma induced in vivo in a BALB/c mouse by the administration of the chemical, 7,12-dimethylbenz(alpha)anthracene. The parental and clonal lines in vitro, as well as tumors derived from them in vivo, maintained an epithelial morphology at the light microscope level. Electron microscopic observations demonstrated the presence of desmosomes and numerous microtubules and microfilaments, but low levels of rough endoplasmic reticulum and Golgi apparatus. Growth characteristics were examined, including saturation density levels and colony-forming ability on plastic and in suspension. None of the in vitro growth parameters was found to correlate with the tumorigenicity of the lines in syngeneic mice or with their ability to produce C- or B-type virions by reverse transcriptase assay. Peroxidase/antiperoxidase (PAP) immunological staining failed to detect virus-specified antigens, MuMTV gp52, Rauscher MuLV gp69/71, or BALB virus-2 gp70, in the cells. Although epithelial in appearance, the parental cell line did not appear to be functionally differentiated in culture as evidenced by a very low level of casein messenger RNA. Passage of the parental cell line in vivo in a lactating mouse failed to activate virus expression, but a few cells in scattered focal areas in the tumor did synthesize casein detectable by PAP staining.
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PMID:Characterization of a 7,12-dimethylbenz(alpha)anthracene-induced BALB/c mouse mammary tumor epithelial cell line. 677 14

Mouse mammary tumor virus (MMTV) encodes a superantigen (SAg) that promotes stable infection and virus transmission. Upon subcutaneous MMTV injection, infected B cells present SAg to SAg-reactive T cells leading to a strong local immune response in the draining lymph node (LN) that peaks after 6 d. We have used the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (AZT) to dissect in more detail the mechanism of SAg-dependent enhancement of MMTV infection in this system. Our data show that no detectable B or T cell response to SAg occurs in AZT pretreated mice. However, if AZT treatment is delayed 1-2 d after MMTV injection, a normal SAg-dependent local immune response is observed on day 6. Quantitation of viral DNA in draining LN of these infected mice indicates that a 4,000-fold increase in the absolute numbers of infected cells occurs between days 2 and 6 despite the presence of AZT. Furthermore MMTV DNA was found preferentially in surface IgG+ B cells of infected mice and was not detectable in SAg-reactive T cells. Collectively our data suggest that MMTV infection occurs preferentially in B cells without SAg involvement and is completed 1-2 d after virus challenge. Subsequent amplification of MMTV infection between days 2 and 6 requires SAg expression and occurs in the absence of any further requirement for reverse transcription. We therefore conclude that clonal expansion of infected B cells via cognate interaction with SAg-reactive T cells is the predominant mechanism for increasing the level of MMTV infection. Since infected B cells display a memory (surface IgG+) phenotype, both clonal expansion and possibly longevity of the virus carrier cells may contribute to stable MMTV infection.
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PMID:Reverse transcriptase-dependent and -independent phases of infection with mouse mammary tumor virus: implications for superantigen function. 752 52

The natural plant products turmeric, beta-carotene, catechin, and betel leaf extract were evaluated for their antitumor effects on mammary tumorigenesis in murine mammary tumor expressing C3H (Jax) mice and in Wistar rats treated with the chemical carcinogen 7-12-dimethylbenz(a)anthracene (DMBA). Administration of turmeric through the diet and of beta-carotene, catechin, and betel leaf extract through the drinking water to virgin female C3H mice resulted in decreased tumor incidence and tumor burden. Administering 5% turmeric in the diet from 2 months of age showed suppression of mammary tumor virus-related reverse transcriptase activity and of preneoplastic changes in the mammary glands. Furthermore, feeding turmeric from 6 months of age resulted in a 100% inhibition of mammary tumors. In the DMBA model of rat mammary tumorigenesis, administration of turmeric, catechin, and betel leaf extract resulted in decreased tumor burden and tumor incidence, and a delay in the onset of mammary tumors.
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PMID:Chemoprevention of mammary tumor virus-induced and chemical carcinogen-induced rodent mammary tumors by natural plant products. 752 4

INT3 is interrupted by retroviral DNA insertion in approximately 18% of primary Czech mouse mammary tumors induced by mouse mammary tumor virus. One consequence of these insertions is the production of a 2.4-kilobase, tumor-specific RNA transcript encoding the entire intracellular domain of the Int3 protein which is initiated from the 3' long terminal repeat promoter of the inserted viral genome. Female mice (FVB-3) transgenic for a genomic fragment comprised of this truncated region of INT3 express the 2.4-kilobase truncated INT3 transcript and exhibit focal mammary tumors at 100% penetrance. INT3 is a member of a family of genes, highly conserved through evolution and characterized by Drosophila melanogaster Notch and Caenorhabditis elegans lin-12, the function of which relates to cell fate determination. Upon transfection into the appropriate hosts, expression vectors of truncated Notch and lin-12, representing their respective cytoplasmic domains, have been demonstrated to effect their complete gene function with respect to cell fate determination. This suggests that the extracellular portion of these proteins function only to regulate activity. Reciprocal transplantation of transgenic FVB-3 and normal mammary tissue to the epithelium-divested fat pads of the respective donor females demonstrates that FVB-3 mammary epithelium is unable to grow and/or to functionally differentiate. However, normal epithelium grows and fully differentiates in transgenic FVB-3 fat pads, indicating that the dysfunction of FVB-3 mammary glands is due to a deficiency inherent in their epithelium. Electron microscopy reveals that transgenic INT3 epithelial cells do not form intercellular junctional complexes in the developing subadult mammary gland. The hormonal stimulation of pregnancy overcomes the deficiency for ductal growth so apparent in the virgin gland such that pregnant FVB-3 glands produce complete ductal systems. Nevertheless, during pregnancy, FVB-3 mammary cells fail to form secretory lobules and to produce milk. Examination of INT3 expression by immunocytochemistry and reverse transcriptase-PCR show that INT3 is expressed constitutively in mammary stroma and epithelia at all stages of postpubertal mammary evolution. These results indicate that deregulated expression of a truncated Int3 in mammary epithelial cells limits their capacity to perform the cell fate decisions required for morphogenesis and functional differentiation.
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PMID:Constitutive expression of a truncated INT3 gene in mouse mammary epithelium impairs differentiation and functional development. 754 53

Mineralocorticoid receptors (MRs) are nonselective in vitro, binding corticosterone, cortisol, and aldosterone with similar affinity. In the distal nephron in vivo, MRs are selectively activated by aldosterone despite much higher glucocorticoid levels. This has been suggested to reflect the action of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which catalyzes rapid inactivation of corticosterone to 11-dehydrocorticosterone (cortisol to cortisone). However, cellular models of this effect have not been reported, and a recent study suggested that properties intrinsic to MR contribute to aldosterone selectivity. We have screened clonal mammalian cell lines for 11 beta-HSD activity. Pig kidney epithelial LLC-PK1 cells expressed by far the greatest 11 beta-HSD activity. In cell homogenates, this was NAD-dependent, with Km for corticosterone of 34.4 nM and cortisol of 89.7 nM. Intact LLC-PK1 cells showed similar apparent Km for corticosterone (13.9 nM) and cortisol (79.4 nM); only 11 beta-dehydrogenation was detected. These biochemical data indicate the expression of the type 2 isoform, 11 beta-HSD2. Using primers to conserved regions of 11 beta-HSD2, a reverse transcriptase-polymerase chain reaction product was obtained from LLC-PK1 cell RNA. Sequence analysis revealed close homology to previously cloned 11 beta-HSD2 cDNAs from several species. LLC-PK1 cell 11 beta-HSD activity was inhibited by carbenoxolone (IC50 approximately 10(-8) M) and high concentrations of estradiol or progesterone (10(-7) and 10(-6) M), but was induced at lower estradiol concentrations (10(-8) and 10(-9) M). To examine whether the 11 beta-HSD2 activity in LLC-PK1 cells regulates corticosterone access to MR, cells were transfected with the corticosteroid-inducible mouse mammary tumor virus long terminal repeat-luciferase reporter construct. Cell transfection by a lipofection method did not alter 11 beta-HSD activity in LLC-PK1 cells. LLC-PK1 cells expressed low levels of MR (13.9 fmol/mg protein, dissociation constant (Kd) 0.3 x 10(-9) M for aldosterone) and glucocorticoid receptors (GR; 18.5 fmol/mg protein, Kd 0.3 x 10(-9) M for dexamethasone). Transfection with mouse mammary tumor virus long terminal repeat-luciferase reporter construct alone suggested that the endogenous levels of MR and GR were insufficient to affect transcription. However, cotransfection of LLC-PK1 cells with pRShMR, an MR expression plasmid, allowed at least 50-fold induction of luciferase with 10(-8) M aldosterone; the ED50 0.3 x 10(-9) M closely reflects the in vitro affinity of MR for aldosterone. Corticosterone only weakly induced luciferase (maximum of 6-fold induction).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:LLC-PK1 cells model 11 beta-hydroxysteroid dehydrogenase type 2 regulation of glucocorticoid access to renal mineralocorticoid receptors. 758 9

A macaque CD4 + adherent cell line was generated by stable expression of the human CD4 gene in a rhesus macaque mammary tumor cell line, CMMT. The resulting cell line CMMT/CD4 expressed surface CD4 and was sensitive to infection by a wide range of isolates of simian immunodeficiency virus (SIV) of different subgroups, but was not susceptible to infection with HIV-1. The CMMT/CD4 cell line was used to develop a microassay for measurement of neutralizing antibody in plasma of SIV-infected or immunized animals. Single infected cells could be detected in a monolayer of CMMT/CD4 by immunoperoxidase and a 90% reduction in the number of positive cells was used as a measure of neutralizing activity of two-fold plasma dilutions. This assay had comparable sensitivity to methods based upon detecting a reduction in reverse transcriptase activity of SIV, reduction of viral antigen, or inhibition of cytopathic effect.
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PMID:A macaque adherent cell line that expresses human CD4 is susceptible to SIV: utility for assessing neutralizing antibody. 763 23


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