Expression of Kirsten Murine Sarcoma Virus in Transformed Nonproducer and Revertant NIH/3T3 Cells: Evidence for Cell-mediated Resistance to a Viral Oncogene in Phenotypic Reversion

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1984 May 1

PMID 6323744

Citations 8

Authors

J D Norton

F Cook

P C Roberts

J P Clewley

R J Avery

Affiliations

Soon will be listed here.

Abstract

Expression of the provirus in a clonally related series of Kirsten murine sarcoma virus-transformed NIH/3T3 nonproducer cell lines was examined at both the transcriptional and translational levels. All cells expressed high levels of genome-sized viral RNA with little variation between cell lines despite differences in provirus integration site and copy number. Expression of K-ras RNA was estimated to be at least 10- to 20-fold higher than that of the mouse cellular homolog of the viral transforming gene. Levels of the virus-coded transforming protein, p21, were similarly elevated, with little variation between nonproducer cells. In two revertant cell lines containing a normal provirus and a rescuable transforming gene, no impairment in expression at either the transcriptional or translational level was found. After superinfection with Kirsten murine sarcoma virus, one revertant became more tumorigenic, whereas the other remained nontumorigenic. These results show that cell transformation by Kirsten murine sarcoma virus is invariably associated with elevated expression of the virus-coded oncogene and that one of the revertants is resistant to the action of the viral transforming gene.

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References

Denhardt D . A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966; 23(5):641-6. DOI: 10.1016/0006-291x(66)90447-5. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Temin H . The protovirus hypothesis: speculations on the significance of RNA-directed DNA synthesis for normal development and for carcinogenesis. J Natl Cancer Inst. 1971; 46(2):3-7. View

Stephenson J, Reynolds R, Aaronson S . Characterization of morphologic revertants of murine and avian sarcoma virus-transformed cells. J Virol. 1973; 11(2):218-22. PMC: 355085. DOI: 10.1128/JVI.11.2.218-222.1973. View

Kessler S . Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975; 115(6):1617-24. View

Rigby P, Dieckmann M, Rhodes C, Berg P . Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977; 113(1):237-51. DOI: 10.1016/0022-2836(77)90052-3. View

Bishop J . Retroviruses. Annu Rev Biochem. 1978; 47:35-88. DOI: 10.1146/annurev.bi.47.070178.000343. View

Collett M, Brugge J, Erikson R . Characterization of a normal avian cell protein related to the avian sarcoma virus transforming gene product. Cell. 1978; 15(4):1363-9. DOI: 10.1016/0092-8674(78)90061-2. View

Fan H, Jaenisch R, MacIsaac P . Low-multiplicity infection of Moloney murine leukemia virus in mouse cells: effect on number of viral DNA copies and virus production in producer cells. J Virol. 1978; 28(3):802-9. PMC: 525804. DOI: 10.1128/JVI.28.3.802-809.1978. View

10.

Bondurant M, Ramabhadran R, Green M, Wold W . "sarc" sequence transcription in Moloney sarcoma virus-transformed nonproducer cell lines. J Virol. 1979; 29(1):76-82. PMC: 353076. DOI: 10.1128/JVI.29.1.76-82.1979. View

11.

Krzyzek R, Lau A, Faras A . Nature of Rous sarcoma virus-specific RNA in transformed and revertant field vole cells. J Virol. 1979; 29(2):507-15. PMC: 353183. DOI: 10.1128/JVI.29.2.507-516.1979. View

12.

Oppermann H, Levinson A, Varmus H, LEVINTOW L, Bishop J . Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src). Proc Natl Acad Sci U S A. 1979; 76(4):1804-8. PMC: 383480. DOI: 10.1073/pnas.76.4.1804. View

13.

Porzig K, ROBBINS K, Aaronson S . Cellular regulation of mammalian sarcoma virus expression: a gene regulation model for oncogenesis. Cell. 1979; 16(4):875-84. DOI: 10.1016/0092-8674(79)90102-8. View

14.

Shih T, Weeks M, Young H, Scholnick E . Identification of a sarcoma virus-coded phosphoprotein in nonproducer cells transformed by Kirsten or Harvey murine sarcoma virus. Virology. 1979; 96(1):64-79. DOI: 10.1016/0042-6822(79)90173-9. View

15.

Collett M, Brugge J, Erikson R, Lau A, Krzyzek R, Faras A . The src gene product of transformed and morphologically reverted ASV-infected mammalian cells. Nature. 1979; 281(5728):195-8. DOI: 10.1038/281195a0. View

16.

Trainor C, Reitz Jr M . Loss of proviral DNA sequences in a revertant of Kirsten sarcoma virus-transformed murine fibroblasts. J Gen Virol. 1979; 44(1):245-9. DOI: 10.1099/0022-1317-44-1-245. View

17.

Chien U, Lai M, Shih T, Verma I, Scolnick E, Roy-Burman P . Heteroduplex analysis of the sequence relationships between the genomes of Kirsten and Harvey sarcoma viruses, their respective parental murine leukemia viruses, and the rat endogenous 30S RNA. J Virol. 1979; 31(3):752-60. PMC: 353503. DOI: 10.1128/JVI.31.3.752-760.1979. View

18.

Morris A, Clegg C, Jones J, Rodgers B, Avery R . The isolation and characterization of a clonally related series of murine retrovirus-infected mouse cells. J Gen Virol. 1980; 49(1):105-13. DOI: 10.1099/0022-1317-49-1-105. View

19.

Shih T, Papageorge A, Stokes P, Weeks M, Scolnick E . Guanine nucleotide-binding and autophosphorylating activities associated with the p21src protein of Harvey murine sarcoma virus. Nature. 1980; 287(5784):686-91. DOI: 10.1038/287686a0. View

20.

Thomas P . Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980; 77(9):5201-5. PMC: 350025. DOI: 10.1073/pnas.77.9.5201. View