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. 1996 Jul 1;24(13):2528–2534. doi: 10.1093/nar/24.13.2528

MoMuLV proviral integrations identified by Sup-F selection in tumors from infected myc/pim bitransgenic mice correlate with activation of the gfi-1 gene.

T Schmidt 1, M Zörnig 1, R Beneke 1, T Möröy 1
PMCID: PMC145976  PMID: 8692692

Abstract

Infecting mice with a mutant Moloney murine leukemia virus which contains the bacterial suppressor tRNA supF in its LTR allows rapid cloning of proviral integration sites from genomic tumour DNA. In a previous study Emu pim-1/Emu L-myc bitransgenic mice had been inoculated neonatally with MoMuLV supF virus. The retroviral infection led to acceleration of lymphomagenesis indicating the proviral activation of further oncogenes cooperating with myc and pim-1 in tumour development. Using a functional supF screen for analysis of genomic mouse tumour DNA libraries which had been constructed in the phage vector EMBL3A, a common proviral integration site on mouse chromosome 5 was cloned and found to be identical to the proviral integration site evi-5 which has recently been identified in an AKXD T-cell lymphoma and which is located 18 kb upstream of the gfi-1 gene. Tumours bearing evi-5 integrations showed an enhanced gfi-1 expression level suggesting that gfi-1 is the target gene for insertions at the evi-5 locus. Together with three other previously described Moloney integration clusters all responsible for enhanced gfi-1 expression the number of tumours from infected double transgenic Emu L-myc/Emu pim-1 transgenic mice with retrovirally activated gfi-1 added up to 53% underscoring the role of GFI-1 as an effective collaborator for MYC and PIM-1 in the process of lymphomagenesis.

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Selected References

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  1. Adams J. M., Cory S. Transgenic models for haemopoietic malignancies. Biochim Biophys Acta. 1991 Apr 16;1072(1):9–31. doi: 10.1016/0304-419x(91)90004-5. [DOI] [PubMed] [Google Scholar]
  2. Adams J. M., Cory S. Transgenic models of tumor development. Science. 1991 Nov 22;254(5035):1161–1167. doi: 10.1126/science.1957168. [DOI] [PubMed] [Google Scholar]
  3. Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., Brinster R. L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
  4. Berns A., van der Lugt N., Alkema M., van Lohuizen M., Domen J., Acton D., Allen J., Laird P. W., Jonkers J. Mouse model systems to study multistep tumorigenesis. Cold Spring Harb Symp Quant Biol. 1994;59:435–447. doi: 10.1101/sqb.1994.059.01.049. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  7. Gilks C. B., Bear S. E., Grimes H. L., Tsichlis P. N. Progression of interleukin-2 (IL-2)-dependent rat T cell lymphoma lines to IL-2-independent growth following activation of a gene (Gfi-1) encoding a novel zinc finger protein. Mol Cell Biol. 1993 Mar;13(3):1759–1768. doi: 10.1128/mcb.13.3.1759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Habets G. G., Scholtes E. H., Zuydgeest D., van der Kammen R. A., Stam J. C., Berns A., Collard J. G. Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell. 1994 May 20;77(4):537–549. doi: 10.1016/0092-8674(94)90216-x. [DOI] [PubMed] [Google Scholar]
  9. Hanahan D. Transgenic mice as probes into complex systems. Science. 1989 Dec 8;246(4935):1265–1275. doi: 10.1126/science.2686032. [DOI] [PubMed] [Google Scholar]
  10. Harris A. W., Pinkert C. A., Crawford M., Langdon W. Y., Brinster R. L., Adams J. M. The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells. J Exp Med. 1988 Feb 1;167(2):353–371. doi: 10.1084/jem.167.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haupt Y., Alexander W. S., Barri G., Klinken S. P., Adams J. M. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell. 1991 May 31;65(5):753–763. doi: 10.1016/0092-8674(91)90383-a. [DOI] [PubMed] [Google Scholar]
  12. Haupt Y., Bath M. L., Harris A. W., Adams J. M. bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis. Oncogene. 1993 Nov;8(11):3161–3164. [PubMed] [Google Scholar]
  13. Lammie G. A., Smith R., Silver J., Brookes S., Dickson C., Peters G. Proviral insertions near cyclin D1 in mouse lymphomas: a parallel for BCL1 translocations in human B-cell neoplasms. Oncogene. 1992 Dec;7(12):2381–2387. [PubMed] [Google Scholar]
  14. Lazo P. A., Lee J. S., Tsichlis P. N. Long-distance activation of the Myc protooncogene by provirus insertion in Mlvi-1 or Mlvi-4 in rat T-cell lymphomas. Proc Natl Acad Sci U S A. 1990 Jan;87(1):170–173. doi: 10.1073/pnas.87.1.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Liao X., Buchberg A. M., Jenkins N. A., Copeland N. G. Evi-5, a common site of retroviral integration in AKXD T-cell lymphomas, maps near Gfi-1 on mouse chromosome 5. J Virol. 1995 Nov;69(11):7132–7137. doi: 10.1128/jvi.69.11.7132-7137.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Michiels F., Habets G. G., Stam J. C., van der Kammen R. A., Collard J. G. A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature. 1995 May 25;375(6529):338–340. doi: 10.1038/375338a0. [DOI] [PubMed] [Google Scholar]
  17. Möröy T., Fisher P., Guidos C., Ma A., Zimmerman K., Tesfaye A., DePinho R., Weissman I., Alt F. W. IgH enhancer deregulated expression of L-myc: abnormal T lymphocyte development and T cell lymphomagenesis. EMBO J. 1990 Nov;9(11):3659–3666. doi: 10.1002/j.1460-2075.1990.tb07577.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Möröy T., Verbeek S., Ma A., Achacoso P., Berns A., Alt F. E mu N- and E mu L-myc cooperate with E mu pim-1 to generate lymphoid tumors at high frequency in double-transgenic mice. Oncogene. 1991 Nov;6(11):1941–1948. [PubMed] [Google Scholar]
  19. Reik W., Weiher H., Jaenisch R. Replication-competent Moloney murine leukemia virus carrying a bacterial suppressor tRNA gene: selective cloning of proviral and flanking host sequences. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1141–1145. doi: 10.1073/pnas.82.4.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  21. Suda Y., Aizawa S., Hirai S., Inoue T., Furuta Y., Suzuki M., Hirohashi S., Ikawa Y. Driven by the same Ig enhancer and SV40 T promoter ras induced lung adenomatous tumors, myc induced pre-B cell lymphomas and SV40 large T gene a variety of tumors in transgenic mice. EMBO J. 1987 Dec 20;6(13):4055–4065. doi: 10.1002/j.1460-2075.1987.tb02751.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Verbeek S., van Lohuizen M., van der Valk M., Domen J., Kraal G., Berns A. Mice bearing the E mu-myc and E mu-pim-1 transgenes develop pre-B-cell leukemia prenatally. Mol Cell Biol. 1991 Feb;11(2):1176–1179. doi: 10.1128/mcb.11.2.1176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zörnig M., Klett C., Lovec H., Hameister H., Winking H., Adolph S., Möröy T. Establishment of permanent wild-mouse cell lines with readily identifiable marker chromosomes. Cytogenet Cell Genet. 1995;71(1):37–40. doi: 10.1159/000134057. [DOI] [PubMed] [Google Scholar]
  24. Zörnig M., Schmidt T., Karsunky H., Grzeschiczek A., Möröy T. Zinc finger protein GFI-1 cooperates with myc and pim-1 in T-cell lymphomagenesis by reducing the requirements for IL-2. Oncogene. 1996 Apr 18;12(8):1789–1801. [PubMed] [Google Scholar]
  25. van Lohuizen M., Berns A. Tumorigenesis by slow-transforming retroviruses--an update. Biochim Biophys Acta. 1990 Dec 11;1032(2-3):213–235. doi: 10.1016/0304-419x(90)90005-l. [DOI] [PubMed] [Google Scholar]
  26. van Lohuizen M., Verbeek S., Scheijen B., Wientjens E., van der Gulden H., Berns A. Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991 May 31;65(5):737–752. doi: 10.1016/0092-8674(91)90382-9. [DOI] [PubMed] [Google Scholar]
  27. van der Lugt N. M., Domen J., Linders K., van Roon M., Robanus-Maandag E., te Riele H., van der Valk M., Deschamps J., Sofroniew M., van Lohuizen M. Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 1994 Apr 1;8(7):757–769. doi: 10.1101/gad.8.7.757. [DOI] [PubMed] [Google Scholar]

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