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)

The genetic structure of the McDonough strain of feline sarcoma virus (SM-FeSV) was deduced by analysis of molecularly cloned, transforming proviral DNA. The 8.2-kilobase pair SM-FeSV provirus is longer than those of other feline sarcoma viruses and contains a transforming gene (v-fms) flanked by sequences derived from feline leukemia virus. The order of genes with respect to viral RNA is 5'-gag-fms-env-3', in which the entire feline leukemia virus env gene and an almost complete gag sequence are represented. Transfection of NIH/3T3 cells with cloned SM-FeSV proviral DNA induced foci of morphologically transformed cells which expressed SM-FeSV gene products and contained rescuable sarcoma viral genomes. Cells transformed by viral infection or after transfection with cloned proviral DNA expressed the polyprotein (P170gag-fms) characteristic of the SM-FeSV strain. Two proteolytic cleavage products (P120fms and pp55gag) were also found in immunoprecipitates from metabolically labeled, transformed cells. An additional polypeptide, detected at comparatively low levels in SM-FeSV transformants, was indistinguishable in size and antigenicity from the envelope precursor (gPr85env) of feline leukemia virus. The complexity of the v-fms gene (3.1 +/- 0.3 kilobase pairs) is approximately twofold greater than the viral oncogene sequences (v-fes) of Snyder-Theilen and Gardner-Arnstein FeSV. By heteroduplex, restriction enzyme, and nucleic acid hybridization analyses, v-fms and v-fes sequences showed no detectable homology to one another. Radiolabeled DNA fragments representing portions of the two viral oncogenes hybridized to different EcoRI and HindIII fragments of normal cat cellular DNA. Cellular sequences related to v-fms (designated c-fms) were much more complex than c-fes and were distributed segmentally over more than 40 kilobase pairs in cat DNA. Comparative structural studies of the molecularly cloned proviruses of Synder-Theilen, Gardner-Arnstein, and SM-FeSV showed that a region of the feline-leukemia virus genome derived from the pol-env junction is represented adjacent to v-onc sequences in each FeSV strain and may have provided sequences preferred for recombination with cellular genes.
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PMID:McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms). 628 62

The sequences required for transformation by the Gardner-Arnstein (GA) strain of feline sarcoma virus (GA-FeSV) were defined by site-directed, in vitro mutagenesis of molecularly cloned proviral DNA. Portions of the Ga-FeSV provirus, subcloned in the plasmid pBR322, were mutagenized by deletion or frameshift at XhoI restriction sites flanking the nucleotide sequences presumed to encode the GA-FeSV transforming polyprotein (P108(gag-fes)). The biological activity of subgenomic and reconstructed full-genome-length molecules was assayed by transfection and focus induction in NIH 3T3 cells. Both mutant and wild-type molecules containing the intact P108(gag-fes) coding region induced foci of transformed cells at efficiencies between 10(4) and 10(5) focus-forming units per pmol of DNA; a deletion mutant lacking 3'-terminal v-fes sequences was completely nontransforming in parallel assays. Representative subcloned foci of transformed NIH 3T3 cells synthesized P108(gag-fes) with associated in vitro protein kinase activity. Focus-forming viruses could be rescued from transformed subclones induced by full-length proviral DNA, but not from cells transformed by subgenomic DNA lacking a 3' long terminal repeat (LTR). It was concluded that: (i) nucleotide sequences encoding P108(gag-fes) and its associated kinase activity are responsible for transformation, (ii) the GA-FeSV 3' env and LTR sequences are not required for focus induction, and (iii) the 3' LTR is necessary for rescue of infectious FeSV RNA. A chimeric DNA containing the 5' LTR and P108(gag-fes) coding region of GA-FeSV joined to the 3' LTR of Moloney murine sarcoma virus was both transforming and rescuable at high efficiency. Restriction analysis showed that passaged stocks of rescued transforming virus contained Moloney murine sarcoma virus U3 sequences at both proviral DNA termini, consistent with generally accepted models for LTR formation during reverse transcription. Wild-type GA-FeSV and the chimeric virus (here designated as GAHT), each rescued from NIH 3T3 cells with the same amphotropic murine leukemia virus, yielded approximately equal numbers of foci when titrated on CCL 64 mink cells. By contrast, on mouse NIH 3T3 cells, the focus-forming titer of GAHT was 1 to 2 log higher than that of FeSV. The foci induced on NIH 3T3 cells by GAHT appeared earlier and were reproducibly larger than those induced by GA-FeSV. Differences in transforming activity on NIH 3T3 cells were also found using colony formation in agar, showing that the more rapid appearance and larger size of foci formed in liquid media were not due to virus spread. These data suggest that transcriptional control signals within the viral LTR regulate the levels of the transforming gene product in a species-specific manner.
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PMID:Mutant feline sarcoma proviruses containing the viral oncogene (v-fes) and either feline or murine control elements. 630 Apr 43

A new acute transforming type C retrovirus was isolated from mice inoculated with a virus stock obtained by iododeoxyuridine induction of methylcholanthrene-transformed C3H/10T1/2 mouse cells. This virus, designated 3611-MSV, transforms embryo fibroblasts and epithelial cells in culture and induces fibrosarcomas in vivo. 3611-MSV is replication defective, requiring a type C helper virus for propagation both in vitro and in vivo. By using endpoint transmission of 3611-MSV to MMCE C17 mouse and FRE 3A rat cells, several nonproductively transformed clonal cell lines have been derived. Pseudotype virus stocks obtained from such clones transform cells in vitro, are highly oncogenic in vivo, and exhibit host range and serological properties that are characteristic of their helper virus component. Analysis of viral antigen expression in 3611-MSV-transformed cells has led to the demonstration of a 90,000-molecular-weight (Mr) polyprotein and a 75,000-Mr probable cleavage product, both containing the amino-terminal murine leukemia virus gag gene proteins p15 and p12. In contrast to gene products of many previously described mammalian transforming viruses, 3611-MSV-encoded polyproteins lack detectable protein kinase activity, and 3611-MSV-transformed cells resemble chemically transformed cell line C3H/MCA-5, from which 3611-MuLV was originally derived, in that they do not exhibit elevated levels of phosphotyrosine. By using molecular hybridization the 3611-MSV transforming gene was found to be distinct from previously described mammalian cellular oncogenic sequences, including c-ras, c-abl, c-fes, c-fms, c-sis, and c-mos.
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PMID:New mammalian transforming retrovirus: demonstration of a polyprotein gene product. 630 Apr 62

The Gardner (GA) and Snyder-Theilen (ST) isolates of feline sarcoma virus (FeSV) represent genetic recombinants between feline leukemia virus (FeLV) and transformation-specific sequences (v-fes gene) of cat cellular origin. A related transforming gene (v-fps), common to the Fujinami, PRC II, and UR 1 strains of avian sarcoma virus has also been described. Translational products of each of these recombinant virus isolates are expressed in the form of polyproteins exhibiting protein kinase activities with specificity for tyrosine residues. In the present study, v-fes and v-fps homologous sequences of GA-FeSV, ST-FeSV, and Fujinami sarcoma virus (FSV) are defined and these independently derived transforming genes are shown to correspond to a common cellular genetic locus which has remained highly conserved throughout vertebrate evolution.
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PMID:Transforming genes of avian (v-fps) and mammalian (v-fes) retroviruses correspond to a common cellular locus. 630 Nov 50

We have identified the oncogene and the putative transforming protein of the Parodi-Irgens feline sarcoma virus (PI-FeSV). The PI-FeSV is defective and needs a helper virus for its replication. The v-onc sequences in the PI-FeSV were found to be related to the v-sis sequences of the simian sarcoma virus (SSV). PI-FeSV nonproducer cells express two viral RNAs, a 6.8-and a 3.3-kilobase RNA. The 6.8-kilobase RNA contains gag, sis, and env sequences but lacks the pol gene. The 3.3-kilobase RNA, on the other hand, contains only env sequences. We have detected one feline leukemia virus-related protein product in these cells, namely, a 76-kilodalton protein which contains determinants of the feline leukemia virus gag proteins p15 and p30. The v-sis sequences in the PI-FeSV have been located near the 5' end of the viral genome. Taken together, these results imply that the p76 protein contains both feline leukemia virus gag and sis sequences and probably is the transforming protein of this virus. In contrast, in SSV the sis sequences are located towards the 3' end of the viral genome, and the sis protein is thought to be expressed via a subgenomic RNA. PI-FeSV and SSV therefore use different schemes to express their onc-related sequences. The v-sis sequences in the PI-FeSV contain restriction sites which reflect the different origin of the v-sis sequences in the PI-FeSV and SSV. The homologous oncogenes of the PI-FeSV and SSV thus were transduced by two different retroviruses, feline leukemia virus and the simian sarcoma-associated virus, apparently from the genomes of different species.
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PMID:The Parodi-Irgens feline sarcoma virus and simian sarcoma virus have homologous oncogenes, but in different contexts of the viral genomes. 630 23

Mink cells morphologically transformed by either Snyder-Theilen feline sarcoma virus (ST-FeSV) or Abelson murine leukemia virus (Abelson-MuLV) exhibit relatively high rates of reversion to the nontransformed phenotype. The proviral DNAs are conserved within the revertant lines and have not undergone changes in integration sites due to translocations or other genomic rearrangements. In contrast, expression of well-defined viral-encoded transforming proteins is blocked and elevated levels of phosphotyrosine characteristic of the parental transformed cells are reduced to control levels. Loss of the transformed phenotype is associated with increased cytosine methylation of proviral DNA sequences while levels of methylation resume control levels upon spontaneous retransformation of revertant clones. Following molecular cloning, and transfection to Rat-2 cells, ST-FeSV proviral DNAs from revertant and transformed cells induced similar numbers of transformed foci. Cytosine methylation sites involved in regulation of expression of the major ST-FeSV encoded transforming protein have been localized within the proviral DNA itself rather than in adjacent cellular flanking sequences. In contrast to the v-fes proviral DNA, c-fes, the cellular homolog of the ST-FeSV acquired transforming sequences, is highly methylated in cytosine residues in both transformed and revertant clones. These findings demonstrate regulation of viral oncogene-mediated transformation by cytosine methylation and suggest that expression of cellular homologs of viral oncogenes, such as c-fes, are also subject to regulation at this level.
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PMID:Regulation of viral and cellular oncogene expression by cytosine methylation. 630 83

Snyder-Theilen feline sarcoma virus (ST-FeSV) codes for a protein kinase with specificity for tyrosine residues (Barbacid et al., Proc. Natl. Acad. Sci. U.S.A. 77:5158-5163, 1980), properties analogous to those of the transforming gene product of Abelson murine leukemia virus (Witte et al., Nature (London) 283:826-831, 1980). In the present report, ST-FeSV was demonstrated to transform murine hematopoietic cells under in vitro assay conditions which detect lymphoid cell transformation by Abelson murine leukemia virus. Bone marrow colony formation was shown to require ST-FeSV, follow single-hit kinetics, and require the presence of mercaptoethanol in the agar medium. ST-FeSV-induced colonies could be established in culture as continuous cell lines that demonstrated unrestricted self-renewal capacity and leukemogenicity in vivo. The hematopoietic blast cells transformed by ST-FeSV in culture appeared to be at an early stage of B cell differentiation. They possessed Lyb 2 surface antigens, were dependent on mercaptoethanol for growth, and contained only low levels of terminal deoxynucleotidyl transferase. Moreover, a large fraction of the lines synthesized immunoglobulin mu chain in the absence of light chains. Thus, the phenotype of ST-FeSV hematopoietic transformants was indistinguishable from that of the pre-B lymphoblast transformants induced by Abelson murine leukemia virus. These findings indicate that the in vitro functional similarities in the onc gene products of ST-FeSV and Abelson murine leukemia virus may reflect a common pathway by which they exert their oncogenic potential.
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PMID:In vitro transformation of murine pre-B lymphoid cells by Snyder-Theilen feline sarcoma virus. 630 54

The efficiency was examined of immunization with feline leukemia virus glycoprotein complexes (gp85 rosettes) to protect cats against tumors induced by feline sarcoma virus (FeSV). The glycoprotein was isolated from feline leukemia virus (FeLV). Young cats were vaccinated with the purified viral glycoprotein and challenged with FeSV (FeLV). FeLV gp85 antibody levels were measured by enzyme-linked immunosorbent assay and tumor volumes were determined. In immunized animals tumor development was reduced. Gp85 antibody levels before challenge were correlated inversely with tumor size (r2 = 0.79). This method appears to be suitable for fast and efficient testing of future FeLV vaccines.
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PMID:Active immunization with feline leukemia virus envelope glycoprotein suppresses growth of virus-induced feline sarcoma. 630 80

There is substantial evidence that oncogenes (v-onc) of acute transforming retroviruses have been acquired by transduction of cellular genes (c-onc) with retroviruses. Feline leukaemia virus (FeLV)-associated feline fibrosarcomas have proven to be extremely useful for the isolation of acute transforming retroviruses of a mammalian species. Three different v-onc genes have been identified in five acute transforming feline retroviruses. The Susan McDonough feline sarcoma virus (SMFeSV) contains the oncogene fms (ref. 4). The Snyder-Theilen (ST) and Gardner-Arnstein (GA) FeSVs contain the oncogene fes (ref. 4), which is homologous to the oncogene fps of the avian sarcoma viruses FSV, RRCII, PRCIV and 16L (refs 7, 8). The v-onc sequences of the Parodi-Irgens (PI) FeSV have recently been found to be homologous with the v-sis sequences of the simian sarcoma virus. We report here the isolation of another acute transforming feline retrovirus from a naturally occurring feline fibrosarcoma, designated the Hardy-Zuckerman 2 feline sarcoma virus (HZ2-FeSV) and demonstrate that the HZ2-FeSV and Abelson murine leukaemia virus (A-MuLV) have homologous oncogenes.
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PMID:The Hardy-Zuckerman 2-FeSV, a new feline retrovirus with oncogene homology to Abelson-MuLV. 630 69

Humoral and cellular cytotoxic immune mechanisms of cats were compared against feline leukemia virus (FeLV)- and feline sarcoma virus (FeSV)-transformed cells. The groups of animals studied were nonexposed control cats; FeLV-infected immune or viremic tumor-bearing cats; FeSV-inoculated tumor progressor or regressor cats, and cats immunized with FeSV-transformed autochthonous fibroblasts (ATF). Sera containing complement-dependent antibodies (CDA), which lysed FeLV-producer lymphoma lines, had no cytotoxic effects when tested against FeLV-producer FeSV-transformed fibroblasts. Sera with lytic CDA activity were also tested for antibody-dependent cellular cytotoxic (ADCC) effects with peripheral blood lymphocytes (PBL) from nonimmune cats. No ADCC activity was detected against either lymphoid or fibroblast target lines. To demonstrate that cat PBL contained ADCC effector cells, antibody-coated murine target cells were employed and positive results obtained. Natural killer (NK) assays were performed using PBL from normal and tumor-bearing cats. Cytotoxic effects were only detectable to FeLV-producer lymphomas, and comparable levels of NK activity were found in normal and lymphoid tumor-bearing animals. In cats immunized with ATF, a population of effector cells was found in peripheral blood which had functional characteristics of cytotoxic T lymphocytes (CTL). The killing of ATF by CTL-like cells was not inhibited by FeLV/FeSV immune sera or by sera from autochthonous immune cats. The comparative importance of humoral and cellular cytotoxic mechanisms against FeLV- and FeSV-induced tumors is discussed.
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PMID:Feline cytotoxic immune mechanisms against virus-associated leukemia and fibrosarcoma. 631 39


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