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S R Tronick

Publications and source records attributed to S R Tronick.

At least 55 records · Page 3Linked to original sources
PubMed1986

Molecular cloning and physical characterization of integrated equine infectious anemia virus: molecular and immunologic evidence of its close relationship to ovine and caprine lentiviruses.

Molecular clones of the integrated form of the genome of equine infectious anemia virus (EIAV), the etiologic agent of a naturally occurring, worldwide disease of horses, were obtained. The restriction map of a full-length genome was determined. Additional evidence for the close evolutionary relationship between EIAV and a prototype lentivirus (caprine arthritis encephalitis virus) was acquired by Southern blotting and immunological analyses. An interspecies radioimmunoassay was developed in which EIAV and ovine and caprine lentiviruses could be detected equally well. These studies make available precisely defined reagents to pursue the study of the mechanisms of pathogenesis of lentiviral induced diseases.

Animals↗
PubMed1986

Nucleotide sequence analysis of the long terminal repeat of integrated caprine arthritis encephalitis virus.

The nucleotide sequence of the long terminal repeat (LTR) of caprine arthritis encephalitis virus (CAEV), a prototype lentivirus was determined. 6-bp directly repeated host cell sequences flank the 376-bp proviral LTRs. By comparison with other retroviral sequences, the CAEV LTR likely contains U3, R and U5 regions 207, 86 and 83 base-pairs in length, respectively. Sequences conforming to consensus transcriptional promoter sites were identified in the U3 region upstream of a potential transcription initiation site. A consensus polyadenylation signal is present 20 bases upstream of the putative R-U5 border and a potential poly(A) addition site. Sequence comparisons of the CAEV LTR with those of other retroviruses uncovered significant similarities with that of visna virus. No other global homologies with other retrovirus LTRs could be detected. CAEV utilizes a primer binding site complementary to lysine tRNA as does visna, AIDS associated retroviruses, and mouse mammary tumor virus. The putative primer for positive-strand DNA synthesis identified in the CAEV sequence is identical to that of visna virus and very similar to those of AIDS retroviruses and MMTV. In addition, a stretch that includes the TATA box of the CAEV LTR resembles closely the corresponding region in the AIDS retrovirus. These and other findings further strengthen the classification of AIDS retrovirus as a lentivirus.

Animals↗
PubMed1986

Activated N-ras in a human rectal carcinoma cell line associated with clonal homozygosity in myb locus-restriction fragment polymorphism.

An N-ras transforming gene was detected in human rectal carcinoma-derived cells (7060) and molecularly cloned. The genetic lesion responsible for the transforming activity of the 7060 oncogene was localized to a single nucleotide transition from A to T in codon 61 of the predicted protein. This lesion in the second exon results in substitution of histidine for glutamine at this position. We also found an EcoRI restriction fragment length polymorphism, consisting of two alleles, of the human c-myb gene. The 7060-transformed epithelial cells showed the homozygous phenotype, while normal fibroblasts of the same patient showed the heterozygous phenotype. This suggests a relationship between the phenotypic change in the c-myb locus and the induction of the 7060 tumor.

Carcinoma↗
PubMed1985

A new class of endogenous human retroviral genomes.

Human DNA contains multiple copies of a novel class of endogenous retroviral genomes. Analysis of a human recombinant DNA clone (HLM-2) containing one such proviral genome revealed that it is a mosaic of retroviral-related sequences with the organization and length of known endogenous retroviral genomes. The HLM-2 long terminal repeat hybridized with the long terminal repeat of the squirrel monkey virus, a type D retrovirus. The HLM-2 gag and pol genes share extensive nucleotide sequence homology with those of the M432 retrovirus (a type A-related retrovirus), mouse mammary tumor virus (a type B retrovirus), and the avian Rous sarcoma virus (a type C retrovirus). Nucleotide sequence analysis revealed regions in the HLM-2 pol gene that were as much as 70 percent identical to the mouse mammary tumor virus pol gene. A portion of the putative HLM-2 env gene hybridized with the corresponding region of the M432 viral genome.

Amino Acid Sequence↗
PubMed1985

Chromosomal localization of three human ras genes by in situ molecular hybridization.

Three human ras family protooncogenes, c-Ki-ras-1, and c-Ki-ras-2, and N-ras, have been mapped to chromosome bands 6p11-12, 12p11.1-12.1, and 1p11-13, respectively by in situ molecular hybridization. Certain human cancers display consistent and specific alterations involving chromosomes 1, 6, and 12. The precise chromosomal localization of ras genes will permit evaluation of the possible effect of these chromosome changes on the structure and activities of ras protooncogenes in human neoplasia.

Chromosome Mapping↗
PubMed1985

Molecular cloning of integrated caprine arthritis-encephalitis virus.

A full-length DNA clone of the exogenous retrovirus, caprine arthritis-encephalitis virus (CAEV), was isolated from high molecular weight DNA of CAEV-infected Himalayan tahr ovary cells. Although other restriction maps of CAEV have been published, this is the first time that the proviral DNA has been cloned. The restriction enzyme map of the clone was determined and found to be identical to that of unintegrated linear CAEV DNA except for the presence of cellular flanking sequences. These findings establish that lentiviruses are able to integrate within the infected host cellular genome. The cloned CAEV genome was shown to contain terminal repeats of approximately 450 base pairs in length, and its restriction enzyme map was oriented with respect to the direction of viral RNA transcription. When the cloned CAEV DNA was used as a molecular probe, it failed to detect related proviral sequences in the genomes of a variety of vertebrate species, including the goat, sheep, horse, mouse, and man. When CAEV DNA was hybridized under relaxed conditions to a variety of cloned DNAs, representing different oncoviral genera, homology to mouse mammary tumor virus (MMTV) was observed, while no homology to avian type C or mammalian type A, C, and D retroviruses was detected. This homology was localized to a region in MMTV corresponding to the 3' end of the gag gene and the 5' end of the pol gene.

Animals↗
PubMed1985

Frequency of molecular alterations affecting ras protooncogenes in human urinary tract tumors.

Members of the ras gene family are activated as oncogenes in many different human cancers. To systematically determine the frequency at which such genes might be involved in the neoplastic process affecting a specific target tissue, urothelial cells, we surveyed a large series of urinary tract tumors for ras oncogenes by DNA transfection and by molecular genetic analysis. Harvey (Ha)-ras oncogenes were detected in 2 of 38 tumors by transfection, molecularly cloned in biologically active form, and shown to contain single base changes at codon 61 leading to substitutions of arginine and leucine, respectively, for glutamine at this position. One additional Ha-ras oncogene was identified in a bladder carcinoma by restriction polymorphisms at codon 12. In one of 21 tumors, we observed a 40-fold amplification of the Kirsten (Ki)-ras gene. No amplification of other ras genes was detected in any of the tumors analyzed. Our findings strengthen the conclusion that codons 12 and 61 are the major "hot spots" of ras oncogene activation and suggest that quantitative alterations in expression due to gene amplification may provide an alternative mechanism for ras gene activation in primary human tumors.

Base Sequence↗
PubMed1985

Isolation and chromosomal localization of the human fgr protooncogene, a distinct member of the tyrosine kinase gene family.

The cell-derived domain of Gardner-Rasheed feline sarcoma virus (GR-FeSV) consists of a gamma-actin- and a tyrosine-specific protein kinase-encoding sequence designated v-fgr. By utilizing a v-fgr probe, it was possible to detect related sequences present at low copy number in DNAs of a variety of mammalian species and to isolate a human fgr homologue. Comparative studies revealed that this human DNA clone represented all but 200 base pairs of v-fgr. Analysis of human genomic DNA demonstrated that the fgr protooncogene was distinct from the cellular homologues of other retrovirus onc genes. In addition, the fgr protooncogene was localized to the distal portion of the short arm of human chromosome 1 at p36.1-36.2 by in situ hybridization. Taken together, our findings establish that the fgr protooncogene is a unique member of the tyrosine kinase gene family.

Actins↗
PubMed1985

Nucleotide sequence analysis of the BALB/c murine sarcoma virus transforming gene.

We determined the nucleotide sequence of the v-H-ras-related oncogene of BALB/c murine sarcoma virus. This oncogene contains an open reading frame of 189 amino acids that initiates and terminates entirely within the mouse cell-derived ras sequence. The protein encoded by this open reading frame matches the sequence predicted for the T24 human bladder carcinoma oncogene product, p21, in all but two positions. The presence of a lysine residue in position 12 of BALB/c murine sarcoma virus p21 likely accounts for its oncogenic properties.

Animals↗
PubMed1984

Major pol gene progenitors in the evolution of oncoviruses.

The genetic relationships among molecularly cloned prototype viruses representing all of the major oncovirus genera were investigated by molecular hybridization and nucleotide sequence analysis. One of the major progenitors of the pol genes of such viruses gives rise to mammalian type C viruses and another gives rise to type A, B, D, and avian type C oncoviruses. Evidence of unusual patterns of homology among the env genes of mammalian type C and D oncoviruses illustrates that genetic interactions between their progenitors contributed to the evolution of oncoviruses.

Amino Acid Sequence↗
PubMed1984

Expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation.

The human sis proto-oncogene contains the coding sequence for one of two polypeptide chains present in preparations of biologically active human platelet-derived growth factor (PDGF). A human clone, c-sis clone 8, which contains all of the v-sis-related sequences present in human DNA, was transcriptionally inactive when transfected into NIH/3T3 cells. When placed under the control of a retrovirus LTR, the clone was transcribed at levels comparable to that observed in cells transformed by SSV DNA. However, c-sis clone 8 DNA did not express detectable sis/PDGF-2 proteins and lacked biologic activity. A putative upstream exon was identified by its ability to detect the 4.2 kb sis-related transcript in certain human cells. When this sequence was inserted in the proper orientation between the LTR and c-sis clone 8, the chimeric molecule acquired high titered transforming activity, comparable to that of SSV DNA. Transformants containing this construct expressed human sis/PDGF-2 translational products. Thus the normal coding sequence for a human growth factor has transforming activity when expressed in an appropriate assay cell.

Amino Acid Sequence↗
PubMed1984

Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor.

The simian sarcoma virus transforming gene, v-sis, encodes a protein, p28sis , that is closely related to human platelet-derived growth factor (PDGF). The human locus related to v-sis was cloned and shown to contain at least five exons corresponding to the v-sis coding region. Nucleotide sequence analysis of these exons revealed that the predicted amino acid sequence of human c-sis differed by 6% from that of the woolly monkey-derived v-sis. These findings imply that the sis proto-oncogene has been well conserved during primate evolution. By comparison of the known amino acid sequences of PDGF peptides with the predicted human c-sis protein, it was possible to demonstrate that this human proto-oncogene is the structural gene encoding one of the two major polypeptides of this potent mitogen for connective tissue cells.

Base Sequence↗
PubMed1984

Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells.

An N-ras-related transforming gene was detected in the human lung carcinoma cell line SW-1271 and molecularly cloned. The lesion responsible for its acquisition of transforming activity was localized to a single nucleotide transition from A to G in codon 61 of the predicted protein. This lesion in the second exon results in the substitution of arginine for glutamine at this position. These findings, together with previous studies, indicate that the activation of ras oncogenes in human tumors is most commonly due to point mutations at one of two major "hot spots" in the ras coding sequence.

Amino Acid Sequence↗