Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1990 Sep;64(9):4043–4050. doi: 10.1128/jvi.64.9.4043-4050.1990

Altered mouse mammary tumor virus transcript synthesis in T-cell lymphoma cells.

J Racevskis 1
PMCID: PMC247865  PMID: 1696633

Abstract

Proviral copies of mouse mammary tumor virus (MMTV) are known to be amplified in certain T-cell lymphomas. Transcription of the amplified MMTV proviruses was studied in detail in two T-cell lymphoma lines and showed the production of deletions and premature termination of env mRNAs and the premature termination of gag transcripts. EL-4 cells produce three env mRNAs, and sequence analysis of cDNAs of the two smaller transcripts revealed large deletions encompassing the 3' half of the env gene. The deletion in at least one of the altered transcripts appeared to be produced by a splicing mechanism. T-cell lymphoma line ML of DBA/2 mice also synthesizes two smaller env transcripts, both of which result from premature termination of transcription. Both lines transcribe high levels of gag mRNAs of about 0.8 kilobases in length, terminating at the end of the region encoding MMTV phosphoprotein pp21. Restriction enzyme BamHI analysis of the amplified proviruses of EL-4 and ML cells as well as of additional non-mammary tumor cell types containing amplified MMTV proviruses suggested that the amplified proviruses were derived from exogenous viruses, or activated endogenous provirus MTV-1 in the case of DBA/2 strain tumor cells.

Full text

PDF
4046

Images in this article

4044Image
on p.4044
4045Image
on p.4045
4046Image
on p.4046
4047Image
on p.4047

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ball J. K., Diggelmann H., Dekaban G. A., Grossi G. F., Semmler R., Waight P. A., Fletcher R. F. Alterations in the U3 region of the long terminal repeat of an infectious thymotropic type B retrovirus. J Virol. 1988 Aug;62(8):2985–2993. doi: 10.1128/jvi.62.8.2985-2993.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
  3. Brookes S., Placzek M., Moore R., Dixon M., Dickson C., Peters G. Insertion elements and transitions in cloned mouse mammary tumour virus DNA: further delineation of the poison sequences. Nucleic Acids Res. 1986 Nov 11;14(21):8231–8245. doi: 10.1093/nar/14.21.8231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen J. C., Shank P. R., Morris V. L., Cardiff R., Varmus H. E. Integration of the DNA of mouse mammary tumor virus in virus-infected normal and neoplastic tissue of the mouse. Cell. 1979 Feb;16(2):333–345. doi: 10.1016/0092-8674(79)90010-2. [DOI] [PubMed] [Google Scholar]
  5. Crouse C. A., Pauley R. J. Molecular cloning and sequencing of the MTV-1 LTR: evidence for a LTR sequence alteration. Virus Res. 1989 Feb;12(2):123–137. doi: 10.1016/0168-1702(89)90059-2. [DOI] [PubMed] [Google Scholar]
  6. Dickson C., Peters G. Proteins encoded by mouse mammary tumour virus. Curr Top Microbiol Immunol. 1983;106:1–34. doi: 10.1007/978-3-642-69357-1_1. [DOI] [PubMed] [Google Scholar]
  7. Dudley J. P., Arfsten A., Hsu C. L., Kozak C., Risser R. Molecular cloning and characterization of mouse mammary tumor proviruses from a T-cell lymphoma. J Virol. 1986 Jan;57(1):385–388. doi: 10.1128/jvi.57.1.385-388.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dudley J., Risser R. Amplification and novel locations of endogenous mouse mammary tumor virus genomes in mouse T-cell lymphomas. J Virol. 1984 Jan;49(1):92–101. doi: 10.1128/jvi.49.1.92-101.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Elliott J. F., Pohajdak B., Talbot D. J., Shaw J., Paetkau V. Phorbol diester-inducible, cyclosporine-suppressible transcription from a novel promoter within the mouse mammary tumor virus env gene. J Virol. 1988 Apr;62(4):1373–1380. doi: 10.1128/jvi.62.4.1373-1380.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fasel N., Buetti E., Firzlaff J., Pearson K., Diggelmann H. Nucleotide sequence of the 5' noncoding region and part of the gag gene of mouse mammary tumor virus; identification of the 5' splicing site for subgenomic mRNAs. Nucleic Acids Res. 1983 Oct 25;11(20):6943–6955. doi: 10.1093/nar/11.20.6943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  12. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  13. Hizi A., Henderson L. E., Copeland T. D., Sowder R. C., Krutzsch H. C., Oroszlan S. Analysis of gag proteins from mouse mammary tumor virus. J Virol. 1989 Jun;63(6):2543–2549. doi: 10.1128/jvi.63.6.2543-2549.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hsu C. L., Fabritius C., Dudley J. Mouse mammary tumor virus proviruses in T-cell lymphomas lack a negative regulatory element in the long terminal repeat. J Virol. 1988 Dec;62(12):4644–4652. doi: 10.1128/jvi.62.12.4644-4652.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kraft R., Ishizaka S. T., Okenquist S. A., Childs G., Lilly F., Lenz J. Absence of mouse mammary tumor virus proviral amplification in chemically induced lymphomas of RF/J mice. J Virol. 1989 Jul;63(7):3200–3204. doi: 10.1128/jvi.63.7.3200-3204.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kwon B. S., Weissman S. M. Mouse mammary tumor virus-related sequences in mouse lymphocytes are inducible by 12-O-tetradecanoyl phorbol-13-acetate. J Virol. 1984 Dec;52(3):1000–1004. doi: 10.1128/jvi.52.3.1000-1004.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee W. T., Prakash O., Klein D., Sarkar N. H. Structural alterations in the long terminal repeat of an acquired mouse mammary tumor virus provirus in a T-cell leukemia of DBA/2 mice. Virology. 1987 Jul;159(1):39–48. doi: 10.1016/0042-6822(87)90345-x. [DOI] [PubMed] [Google Scholar]
  18. Michalides R., Wagenaar E., Hilkens J., Hilgers J., Groner B., Hynes N. E. Acquisition of proviral DNA of mouse mammary tumor virus in thymic leukemia cells from GR mice. J Virol. 1982 Sep;43(3):819–829. doi: 10.1128/jvi.43.3.819-829.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Michalides R., Wagenaar E. Site-specific rearrangements in the long terminal repeat of extra mouse mammary tumor proviruses in murine T-cell leukemias. Virology. 1986 Oct 15;154(1):76–84. doi: 10.1016/0042-6822(86)90431-9. [DOI] [PubMed] [Google Scholar]
  20. Michalides R., Wagenaar E., Weijers P. Rearrangements in the long terminal repeat of extra mouse mammary tumor proviruses in T-cell leukemias of mouse strain GR result in a novel enhancer-like structure. Mol Cell Biol. 1985 Apr;5(4):823–830. doi: 10.1128/mcb.5.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Michalides R., van Nie R., Nusse R., Hynes N. E., Groner B. Mammary tumor induction loci in GR and DBAf mice contain one provirus of the mouse mammary tumor virus. Cell. 1981 Jan;23(1):165–173. doi: 10.1016/0092-8674(81)90281-6. [DOI] [PubMed] [Google Scholar]
  22. Moore R., Dixon M., Smith R., Peters G., Dickson C. Complete nucleotide sequence of a milk-transmitted mouse mammary tumor virus: two frameshift suppression events are required for translation of gag and pol. J Virol. 1987 Feb;61(2):480–490. doi: 10.1128/jvi.61.2.480-490.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morley K. L., Toohey M. G., Peterson D. O. Transcriptional repression of a hormone-responsive promoter. Nucleic Acids Res. 1987 Sep 11;15(17):6973–6989. doi: 10.1093/nar/15.17.6973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nusse R., van der Ploeg L., van Duijn L., Michalides R., Hilgers J. Impaired maturation of mouse mammary tumor virus precursor polypeptides in lymphoid leukemia cells, producing intracytoplasmic A particles and no extracellular B-type virions. J Virol. 1979 Oct;32(1):251–258. doi: 10.1128/jvi.32.1.251-258.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Okayama H., Kawaichi M., Brownstein M., Lee F., Yokota T., Arai K. High-efficiency cloning of full-length cDNA; construction and screening of cDNA expression libraries for mammalian cells. Methods Enzymol. 1987;154:3–28. doi: 10.1016/0076-6879(87)54067-8. [DOI] [PubMed] [Google Scholar]
  27. Peterson D. O., Kriz K. G., Marich J. E., Toohey M. G. Sequence organization and molecular cloning of mouse mammary tumor virus DNA endogenous to C57BL/6 mice. J Virol. 1985 May;54(2):525–531. doi: 10.1128/jvi.54.2.525-531.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Racevskis J., Beyer H. Amplification of mouse mammary tumor virus genomes in non-mammary tumor cells. J Virol. 1989 Jan;63(1):456–459. doi: 10.1128/jvi.63.1.456-459.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Racevskis J. Expression of the protein product of the mouse mammary tumor virus long terminal repeat gene in phorbol ester-treated mouse T-cell-leukemia cells. J Virol. 1986 May;58(2):441–449. doi: 10.1128/jvi.58.2.441-449.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Racevskis J., Sarkar N. H. ML antigen of DBA/2 mouse leukemias: expression of an endogenous murine mammary tumor virus. J Virol. 1982 Jun;42(3):804–813. doi: 10.1128/jvi.42.3.804-813.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Theunissen H. J., Paardekooper M., Maduro L. J., Michalides R. J., Nusse R. Phorbol ester-inducible T-cell-specific expression of variant mouse mammary tumor virus long terminal repeats. J Virol. 1989 Aug;63(8):3466–3471. doi: 10.1128/jvi.63.8.3466-3471.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Verstraeten A. A., van Nie R. Genetic transmission of mammary tumour virus in the DBAf mouse strain. Int J Cancer. 1978 Apr 15;21(4):473–475. doi: 10.1002/ijc.2910210412. [DOI] [PubMed] [Google Scholar]
  35. Wellinger R. J., Garcia M., Vessaz A., Diggelmann H. Exogenous mouse mammary tumor virus proviral DNA isolated from a kidney adenocarcinoma cell line contains alterations in the U3 region of the long terminal repeat. J Virol. 1986 Oct;60(1):1–11. doi: 10.1128/jvi.60.1.1-11.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wheeler D. A., Butel J. S., Medina D., Cardiff R. D., Hager G. L. Transcription of mouse mammary tumor virus: identification of a candidate mRNA for the long terminal repeat gene product. J Virol. 1983 Apr;46(1):42–49. doi: 10.1128/jvi.46.1.42-49.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Young R. A., Davis R. W. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. doi: 10.1073/pnas.80.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van Ooyen A. J., Michalides R. J., Nusse R. Structural analysis of a 1.7-kilobase mouse mammary tumor virus-specific RNA. J Virol. 1983 May;46(2):362–370. doi: 10.1128/jvi.46.2.362-370.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES