Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion

Neel, Benjamin G.; Hayward, William S.; Robinson, Harriet L.; Fang, Joanna; Astrin, Susan M.

doi:10.1016/0092-8674(81)90128-8

Cited by 518 publications

(272 citation statements)

References 44 publications

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“…It indicates therefore that the relatively large amount of viral RNA present in infected avian cells primarily results from increased transcription rather than increased stabilization of viral RNA. It also suggests that the high levels of expression obtained when the ASV LTR is placed upstream of cellular genes either as a result of infection by leukosis virus Neel et al, 1981) or in chimeric plasmids (Gorman et al, 1982) also results predominantly from increased transcription rather than increased stabilization of the RNA. It should be mentioned that in these experiments we did not assay for stability of mRNA beyond 12 h after the actinomycin D addition.…”

Section: Discussionmentioning

confidence: 99%

“…High levels of gene expression are obtained where the ASV long terminal repeat (LTR) is placed upstream of a gene such as bacterial chloramphenicol acetyl transferase (Gorman et al, 1982). The insertion of the avian leukosis LTR upstream of the cellular myc gene results in a higher than normal level of expression of the myc gene RNA and this activation is thought to be involved in the pathogenesis of avian leukosis Neel et al, 1981). However, since steady-state RNA levels were measured in the studies cited above, it is possible that the accumulation of RNA might result wholly or in part from the production of mRNAs which are more stable than the bulk of the cellular mRNAs.…”

Section: Introductionmentioning

confidence: 99%

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Stabilities of Avian Sarcoma Virus RNAs: Comparison of Subgenomic and Genomic Species with Cellular mRNAs

Dimock

Horikami

et al. 1983

Journal of General Virology

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SUMMARYThe stabilities of B77 avian sarcoma virus intracellular RNAs were compared to the stability of the total cellular poly(A)-containing RNA by labelling infected chicken embryo fibroblasts with [3H]uridine for 15 h, adding actinomycin D (1 ~tg per ml) to block further transcription of viral RNA, and selecting virus-specific RNA from the total cellular poly(A)-containing RNA at 3 hourly intervals. The three virus-specific RNA species (9-3, 3.3 and 5.4 kilobases) decayed with half-lives of 7-5, 10, and 15 h, respectively, whereas the bulk of the cellular mRNA decayed with a half-life of 13 h. To correlate these decay rates with the disappearance of mRNA activities, the actinomycin D-treated cells were pulse-labelled with [3H]leucine at 3 hourly intervals after the addition of the drug and virus-specific protein synthesis was assayed by immunoprecipitation. The mRNA activity for the precursor to the non-glycosylated viral structural proteins (Pr76g ag) decayed with a half-life of approximately 6 h, whereas the mRNA activity coding for the precursor to the envelope proteins (gPr92 env) decayed with a half-life of 14 h. Thus, the rate of decay of the individual mRNA species corresponded reasonably well with the decay rate for the synthesis of two of the corresponding gene products. The results indicated that the 5-4 kb env mRNA is more stable under these conditions than the 9.3 kb gag mRNA but was not significantly more stable than the bulk of the cellular mRNA. Virus particle production following the addition of actinomycin D was determined by the reverse transcriptase assay and by the incorporation of viral genomic 70S RNA into extracellular virions. Both assays yielded similar results and indicated that particle production was inhibited at a rate (t~ = 4 h) somewhat faster than the decay of Pr769ag synthesis or the disappearance of 9.3 kb RNA. It was established by two independent methods (pulse and chase, and approach to isotope equilibrium), however, that the intracellular halflife of the RNA that is packaged into virions is 6 to 7 h. Tt~us, these results suggest that a single metabolic pool of 9.3 kb RNA exists in avian sarcoma virus-infected cells and is used both as mRNA and as genome RNA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stabilities of Avian Sarcoma Virus RNAs: Comparison of Subgenomic and Genomic Species with Cellular mRNAs

Dimock

Horikami

et al. 1983

Journal of General Virology

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“…Since VL30 elements are transmissible by retroviruses, they could therefore play a role in MuLVinduced malignant transformation. Thus, a newly integrated VL30 element could cause activation of an adjacent cellular proto-oncogene by a "downstream promotion" mechanism similar to that proposed for some weakly oncogenic retroviruses [26]. The molecular cloning of such retrovirus-transmissible VL30 elements is a first step toward investigating this possibility.…”

Section: Discussionmentioning

confidence: 99%

A novel approach to cloning transcriptionally active retrovirus-like genetic elements from mouse cells

Carter¹,

Norton²,

Avery

1983

Nucl Acids Res

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A family of dispersed, moderately repeated mouse genetic elements is expressed as retrovirus-like 30S RNA species (VL30 RNA) which can be transmitted to other cells when packaged as a pseudovirion complex by murine leukemia viruses (MuLV). Using the endogenous reverse transcriptase reaction of VL30 RNA-containing MuLV particles, full-length VL30 DNA was synthesized and cloned in pAT153. Analysis of a number of clones identified long terminal repeat structures (LTRs) characteristic of retrovirus proviruses and transposable genetic elements. Whilst the unique region of all clones was identical, the LTRs displayed some heterogeneity. Comparison of the unique region of cloned VL30 DNA with mouse genomic VL30 sequences showed the retrovirus-derived clones to be encoded by only a few members of the divergent VL30 gene family. These findings thus demonstrate a method for cloning a defined sub-class of retrovirus-like cellular genes which are both transcriptionally active and transmissible by a retrovirus.

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“…The blots were then prehybridized, hybridized, and washed as previously described (25). Southern blots of human DNAs were probed with the 32P-labeled hu-myc fragment of XhR1-15.…”

Section: Methodsmentioning

confidence: 99%

Structure and expression of the oncogene c-myc in fresh tumor material from patients with hematopoietic malignancies.

Rothberg¹,

Erisman²,

Diehl³

et al. 1984

Mol. Cell. Biol.

110

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c-myc is the cellular gene homologous to the transforming sequence of MC29, an acute avian retrovirus. The human c-myc gene was cloned and used to study the structure and expression of c-myc in a variety of human hematopoietic malignancies. In a careful study of 106 patients, c-myc RNA was found to be expressed at elevated levels in tumor cells of 17 leukemia patients and five lymphoma patients. The c-myc gene was found to be rearranged in two lymphomas, an African Burkitt's lymphoma and a non-Hodgkins lymphoma in leukemic phase. The Burkitt's rearrangement involved the insertion of new DNA sequences upstream from the c-myc 5' coding region, presumably replacing the normal c-myc transcriptional promoter. None of the other 104 patients, including 20 with elevated myc expression, exhibited any evidence of a genetic rearrangement involving the c-myc gene. Our results show that there is a subset of hematopoietic malignancies characterized by elevated expression of c-myc. This elevated expression in most cases is not due to obvious genetic changes (rearrangement, amplification) at the c-myc locus nor to chromosomal translocations in the vicinity of this gene.

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Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion

Cited by 518 publications

References 44 publications

Stabilities of Avian Sarcoma Virus RNAs: Comparison of Subgenomic and Genomic Species with Cellular mRNAs

Stabilities of Avian Sarcoma Virus RNAs: Comparison of Subgenomic and Genomic Species with Cellular mRNAs

A novel approach to cloning transcriptionally active retrovirus-like genetic elements from mouse cells

Structure and expression of the oncogene c-myc in fresh tumor material from patients with hematopoietic malignancies.

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