Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1990 Apr;64(4):1794–1802. doi: 10.1128/jvi.64.4.1794-1802.1990

Insertion mutation of the int-1 and int-2 loci by mouse mammary tumor virus in premalignant and malignant neoplasms from the GR mouse strain.

D W Morris 1, P A Barry 1, H D Bradshaw Jr 1, R D Cardiff 1
PMCID: PMC249317  PMID: 2157060

Abstract

Mouse mammary tumor virus (MMTV)-induced mammary adenocarcinomas can develop from several different premalignant precursors common in GR mice. Insertion mutagenesis of the mammary protooncogenes int-1 and int-2 was studied in this multistep system by analyzing samples from various stages of neoplastic development for novel int-1 and int-2 restriction fragments generated by MMTV provirus integration. int-1 and int-2 insertion mutations were observed in both premalignant lesions and malignant tumors. Some of the tumors with insertion mutations were experimentally derived from insertion mutation-free premalignant precursors. Each class of neoplasm examined had a characteristic frequency of int-1 and int-2 insertion mutations; however, no correspondence was observed between neoplasm morphology and mutation of either gene. These results indicate that insertion mutation of the int-1 and int-2 loci by MMTV provirus can be involved in the earliest identifiable stages of neoplastic development as well as during progression of premalignant lesions to tumors. Insertion mutation of int-1 and int-2 is therefore not stage specific in this system.

Full text

PDF
1794

Images in this article

1796Image
on p.1796
1797Image
on p.1797
1799Image
on p.1799
1800Image
on p.1800

Selected References

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

  1. Cardiff R. D., Fanning T. G., Morris D. W., Ashley R. L., Faulkin L. J. Restriction endonuclease studies of hyperplastic outgrowth lines from BALB/cfC3H mouse hyperplastic mammary nodules. Cancer Res. 1981 Aug;41(8):3024–3029. [PubMed] [Google Scholar]
  2. Cardiff R. D., Morris D. W., Young L. J. Alterations of acquired mouse mammary tumor virus DNA during mammary tumorigenesis in BALB/cfC3H mice. J Natl Cancer Inst. 1983 Nov;71(5):1011–1019. [PubMed] [Google Scholar]
  3. 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]
  4. Cohen J. C., Varmus H. E. Proviruses of mouse mammary tumor virus in normal and neoplastic tissues from GR and C3Hf mouse strains. J Virol. 1980 Aug;35(2):298–305. doi: 10.1128/jvi.35.2.298-305.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DEOME K. B., FAULKIN L. J., Jr, BERN H. A., BLAIR P. B. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res. 1959 Jun;19(5):515–520. [PubMed] [Google Scholar]
  6. DeOme K. B., Medina D. A new approach to mammary tumorigenesis in rodents. Cancer. 1969 Dec;24(6):1255–1258. doi: 10.1002/1097-0142(196912)24:6<1255::aid-cncr2820240632>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  7. Delli Bovi P., Curatola A. M., Kern F. G., Greco A., Ittmann M., Basilico C. An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family. Cell. 1987 Aug 28;50(5):729–737. doi: 10.1016/0092-8674(87)90331-x. [DOI] [PubMed] [Google Scholar]
  8. Dickson C., Smith R., Brookes S., Peters G. Tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2. Cell. 1984 Jun;37(2):529–536. doi: 10.1016/0092-8674(84)90383-0. [DOI] [PubMed] [Google Scholar]
  9. FAULKIN L. J., Jr, DEOME K. B. Regulation of growth and spacing of gland elements in the mammary fat pad of the C3H mouse. J Natl Cancer Inst. 1960 Apr;24:953–969. [PubMed] [Google Scholar]
  10. FOULDS L. The histologic analysis of mammary tumors of mice. J Natl Cancer Inst. 1956 Dec;17(6):701–801. [PubMed] [Google Scholar]
  11. FOULDS L. The natural history of cancer. J Chronic Dis. 1958 Jul;8(1):2–37. doi: 10.1016/0021-9681(58)90039-0. [DOI] [PubMed] [Google Scholar]
  12. Fanning T. G., Puma J. P., Cardiff R. D. Selective amplification of mouse mammary tumor virus in mammary tumors of GR mice. J Virol. 1980 Oct;36(1):109–114. doi: 10.1128/jvi.36.1.109-114.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fanning T. G., Vassos A. B., Cardiff R. D. Methylation and amplification of mouse mammary tumor virus DNA in normal, premalignant, and malignant cells of GR/A mice. J Virol. 1982 Mar;41(3):1007–1013. doi: 10.1128/jvi.41.3.1007-1013.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gallahan D., Callahan R. Mammary tumorigenesis in feral mice: identification of a new int locus in mouse mammary tumor virus (Czech II)-induced mammary tumors. J Virol. 1987 Jan;61(1):66–74. doi: 10.1128/jvi.61.1.66-74.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klein G., Klein E. Evolution of tumours and the impact of molecular oncology. Nature. 1985 May 16;315(6016):190–195. doi: 10.1038/315190a0. [DOI] [PubMed] [Google Scholar]
  16. Kozak C., Peters G., Pauley R., Morris V., Michalides R., Dudley J., Green M., Davisson M., Prakash O., Vaidya A. A standardized nomenclature for endogenous mouse mammary tumor viruses. J Virol. 1987 May;61(5):1651–1654. doi: 10.1128/jvi.61.5.1651-1654.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Majors J. E., Varmus H. E. Nucleotide sequences at host-proviral junctions for mouse mammary tumour virus. Nature. 1981 Jan 22;289(5795):253–258. doi: 10.1038/289253a0. [DOI] [PubMed] [Google Scholar]
  18. Mester J., Wagenaar E., Sluyser M., Nusse R. Activation of int-1 and int-2 mammary oncogenes in hormone-dependent and -independent mammary tumors of GR mice. J Virol. 1987 Apr;61(4):1073–1078. doi: 10.1128/jvi.61.4.1073-1078.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moore R., Casey G., Brookes S., Dixon M., Peters G., Dickson C. Sequence, topography and protein coding potential of mouse int-2: a putative oncogene activated by mouse mammary tumour virus. EMBO J. 1986 May;5(5):919–924. doi: 10.1002/j.1460-2075.1986.tb04304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morris D. W., Bradshaw H. D., Jr, Billy H. T., Munn R. J., Cardiff R. D. Isolation of a pathogenic clone of mouse mammary tumor virus. J Virol. 1989 Jan;63(1):148–158. doi: 10.1128/jvi.63.1.148-158.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mühlbock O. Note on a new inbred mouse-strain GR-A. Eur J Cancer. 1965 Oct;1(2):123–124. doi: 10.1016/0014-2964(65)90003-4. [DOI] [PubMed] [Google Scholar]
  22. Nusse R. The activation of cellular oncogenes by proviral insertion in murine mammary cancer. Cancer Treat Res. 1988;40:283–306. doi: 10.1007/978-1-4613-1733-3_14. [DOI] [PubMed] [Google Scholar]
  23. Nusse R., Varmus H. E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982 Nov;31(1):99–109. doi: 10.1016/0092-8674(82)90409-3. [DOI] [PubMed] [Google Scholar]
  24. Pathak V. K., Strange R., Young L. J., Morris D. W., Cardiff R. D. Survey of int region DNA rearrangements in C3H and BALB/cfC3H mouse mammary tumor system. J Natl Cancer Inst. 1987 Feb;78(2):327–331. [PubMed] [Google Scholar]
  25. Peters G., Brookes S., Smith R., Dickson C. Tumorigenesis by mouse mammary tumor virus: evidence for a common region for provirus integration in mammary tumors. Cell. 1983 Jun;33(2):369–377. doi: 10.1016/0092-8674(83)90418-x. [DOI] [PubMed] [Google Scholar]
  26. Peters G., Lee A. E., Dickson C. Activation of cellular gene by mouse mammary tumour virus may occur early in mammary tumour development. Nature. 1984 May 17;309(5965):273–275. doi: 10.1038/309273a0. [DOI] [PubMed] [Google Scholar]
  27. Peters G., Lee A. E., Dickson C. Concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus. Nature. 1986 Apr 17;320(6063):628–631. doi: 10.1038/320628a0. [DOI] [PubMed] [Google Scholar]
  28. Schuermann M., Michalides R. A rare common integration site of proviruses of the mouse mammary tumor virus in P-type mammary tumors of mouse strain GR. Virology. 1987 Feb;156(2):229–237. doi: 10.1016/0042-6822(87)90402-8. [DOI] [PubMed] [Google Scholar]
  29. Smith D. H., Brutlag D., Friedland P., Kedes L. H. BIONET: national computer resource for molecular biology. Nucleic Acids Res. 1986 Jan 10;14(1):17–20. doi: 10.1093/nar/14.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Varmus H. E. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553–612. doi: 10.1146/annurev.ge.18.120184.003005. [DOI] [PubMed] [Google Scholar]
  31. Yoshida T., Miyagawa K., Odagiri H., Sakamoto H., Little P. F., Terada M., Sugimura T. Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7305–7309. doi: 10.1073/pnas.84.20.7305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. van Ooyen A., Nusse R. Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding domain intact. Cell. 1984 Nov;39(1):233–240. doi: 10.1016/0092-8674(84)90209-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES

  NODES
Note 1
twitter 2