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PMID: 2555789 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Transcriptional activation of cKi-ras proto-oncogene resulting from retroviral promoter insertion.

Nucleic acids research ·Vol. 17 ·No. 22 ·1989-11-25 ·Pages 9259-65

Trusko SP, Hoffman EK, George DL

Abstract

Enhanced expression of the cKi-ras proto-oncogene in a bone marrow-derived mouse cell line, 416B, has been shown to be associated with the integration of Friend viral DNA into the cellular gene. Here we report the results of experiments designed to clarify the molecular mechanism responsible for the cKi-ras overexpression. Based on primer extension analyses and DNA sequencing of cKi-ras cDNA clones, we have obtained evidence that the 416B cells contain viral-host chimaeric transcripts that initiate within the 3' long terminal repeat (LTR) of the integrated provirus. Processing of the transcripts from the rearranged cKi-ras gene includes an unexpected splicing event associated with the fortuitous creation of a cryptic donor splice site at the junction between the proviral and cellular DNA sequences. These data demonstrate that enhanced cKi-ras expression in the 416B cells results from a retroviral promoter insertion mechanism of transcriptional activation.

MeSH Terms
Animals Base Sequence Bone Marrow Cell Line DNA Transposable Elements Exons Female Friend murine leukemia virus/genetics Gene Expression Regulation, Neoplastic Genes, ras Mice Mice, Inbred Strains Molecular Sequence Data Oligonucleotide Probes Promoter Regions, Genetic Proto-Oncogene Mas Transcriptional Activation
Chemicals
DNA Transposable Elements MAS1 protein, human Oligonucleotide Probes Proto-Oncogene Mas
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Trusko S P
Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6072.
Hoffman E K
George D L
References (23)
23 references, click to expand
  1. The syntheiss of high yields of full-length reverse transcripts of globin mRNA.
    Nucleic Acids Res. 1977 Oct;4(10):3455-71 PMID: 73163
  2. Markedly elevated levels of an endogenous sarc protein in a hemopoietic precursor cell line.
    Mol Cell Biol. 1981 Jan;1(1):66-74 PMID: 6821513
  3. Isolation and characterisation of a bipotential haematopoietic cell line.
    Nature. 1979 Feb 8;277(5696):471-4 PMID: 763330
  4. Biological detection of specific mRNA molecules by microinjection.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4503-6 PMID: 291982
  5. Analysis of avian leukosis virus DNA and RNA in bursal tumours: viral gene expression is not required for maintenance of the tumor state.
    Cell. 1981 Feb;23(2):311-22 PMID: 6258797
  6. Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion.
    Cell. 1981 Feb;23(2):323-34 PMID: 6258798
  7. On the mechanism of retrovirus-induced avian lymphoid leukosis: deletion and integration of the proviruses.
    Proc Natl Acad Sci U S A. 1981 Jun;78(6):3418-22 PMID: 6267589
  8. Organization and expression of eucaryotic split genes coding for proteins.
    Annu Rev Biochem. 1981;50:349-83 PMID: 6791577
  9. A catalogue of splice junction sequences.
    Nucleic Acids Res. 1982 Jan 22;10(2):459-72 PMID: 7063411
  10. Mouse cells contain two distinct ras gene mRNA species that can be translated into a p21 onc protein.
    Mol Cell Biol. 1982 Nov;2(11):1339-45 PMID: 6131379
  11. A cellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumour cells.
    Nature. 1983 Jun 9-15;303(5917):497-501 PMID: 6304530
  12. A simple and very efficient method for generating cDNA libraries.
    Gene. 1983 Nov;25(2-3):263-9 PMID: 6198242
  13. Transcriptional interference in avian retroviruses--implications for the promoter insertion model of leukaemogenesis.
    Nature. 1984 Jan 19-25;307(5948):241-5 PMID: 6363938
  14. Molecular analysis of the envelope gene and long terminal repeat of Friend mink cell focus-inducing virus: implications for the functions of these sequences.
    J Virol. 1984 Mar;49(3):828-40 PMID: 6321768
  15. The molecular genetics of cellular oncogenes.
    Annu Rev Genet. 1984;18:553-612 PMID: 6397126
  16. Structure and expression of amplified cKi-ras gene sequences in Y1 mouse adrenal tumor cells.
    EMBO J. 1985 May;4(5):1199-203 PMID: 4006913
  17. Comparison of the transcriptional properties of the Friend and Moloney retrovirus long terminal repeats: importance of tandem duplications and of the core enhancer sequence.
    Virology. 1985 Jul 30;144(2):481-94 PMID: 4060594
  18. Enhanced c-Ki-ras expression associated with Friend virus integration in a bone marrow-derived mouse cell line.
    Proc Natl Acad Sci U S A. 1986 Mar;83(6):1651-5 PMID: 3513183
  19. ras gene Amplification and malignant transformation.
    Mol Cell Biol. 1985 Oct;5(10):2836-41 PMID: 3915535
  20. The molecular genetics of cancer.
    Science. 1987 Jan 16;235(4786):305-11 PMID: 3541204
  21. Structural and functional characterization of the promoter region of the mouse c-Ki-ras gene.
    Mol Cell Biol. 1987 Jul;7(7):2592-6 PMID: 3614201
  22. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
    Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 PMID: 3313277
  23. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
Published
1989-11-25
Pages
9259-65
Language
English
Region
England
NLM ID
0411011
PMCID
PMC335129
Subset
IM
Grants
NCI NIH HHS · CA34462 · United States
NIGMS NIH HHS · GM32592 · United States
Databases
GENBANK
X15887, X15888
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