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. 1991 Aug;65(8):4550–4554. doi: 10.1128/jvi.65.8.4550-4554.1991

Host genetic background effect on the frequency of mouse mammary tumor virus-induced rearrangements of the int-1 and int-2 loci in mouse mammary tumors.

A Marchetti 1, J Robbins 1, G Campbell 1, F Buttitta 1, F Squartini 1, M Bistocchi 1, R Callahan 1
PMCID: PMC248904  PMID: 1712864

Abstract

The frequency with which int-1 and int-2 are rearranged in mouse mammary tumors by mouse mammary tumor virus (MMTV)-induced insertional mutagenesis is a consequence of the host genetic background. In 75% of C3H mammary tumors, int-1 is rearranged by MMTV insertion, whereas only 30% of BALB/cfC3H tumors contain a virus-induced rearrangement of int-1. This difference is significant (P less than 0.005) and could not be accounted for by the potentially additive effect of the genetically transmitted Mtv-1-encoded virus in C3H mice. Similarly, MMTV-induced rearrangement of the int-2 gene in mammary tumors of the R111 mouse strain (59%) occurred at a significantly (P less than 0.025) higher frequency than in BALB/cfR111 (25%) mammary tumors. Moreover, in BALB/cfR111 mammary tumors, there is evidence that rearrangement of int-1 and int-2 does not occur independently (P less than 0.025). These results suggest that the long history of inbreeding for high tumor incidence of C3H and R111 mouse strains has selected for the fixation of host mutations which either complement the action of the particular int gene or affect the sensitivity of specific subpopulations of mammary epithelium to infection by particular strains of MMTV.

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Selected References

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  1. 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]
  2. 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]
  3. Denhardt D. T. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. doi: 10.1016/0006-291x(66)90447-5. [DOI] [PubMed] [Google Scholar]
  4. Dickson C., Peters G. Potential oncogene product related to growth factors. 1987 Apr 30-May 6Nature. 326(6116):833–833. doi: 10.1038/326833a0. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Donehower L. A., Huang A. L., Hager G. L. Regulatory and coding potential of the mouse mammary tumor virus long terminal redundancy. J Virol. 1981 Jan;37(1):226–238. doi: 10.1128/jvi.37.1.226-238.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Etkind P. R. Expression of the int-1 and int-2 loci in endogenous mouse mammary tumor virus-induced mammary tumorigenesis in the C3Hf mouse. J Virol. 1989 Nov;63(11):4972–4975. doi: 10.1128/jvi.63.11.4972-4975.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jakobovits A., Shackleford G. M., Varmus H. E., Martin G. R. Two proto-oncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7806–7810. doi: 10.1073/pnas.83.20.7806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McMahon A. P., Bradley A. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell. 1990 Sep 21;62(6):1073–1085. doi: 10.1016/0092-8674(90)90385-r. [DOI] [PubMed] [Google Scholar]
  10. Michalides R., Verstraeten R., Shen F. W., Hilgers J. Characterization and chromosomal distribution of endogenous mouse mammary tumor viruses of European mouse strains STS/A and GR/A. Virology. 1985 Apr 30;142(2):278–290. doi: 10.1016/0042-6822(85)90336-8. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Muller W. J., Lee F. S., Dickson C., Peters G., Pattengale P., Leder P. The int-2 gene product acts as an epithelial growth factor in transgenic mice. EMBO J. 1990 Mar;9(3):907–913. doi: 10.1002/j.1460-2075.1990.tb08188.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Peters G., Brookes S., Smith R., Placzek M., Dickson C. The mouse homolog of the hst/k-FGF gene is adjacent to int-2 and is activated by proviral insertion in some virally induced mammary tumors. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5678–5682. doi: 10.1073/pnas.86.15.5678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Peters G. Oncogenes at viral integration sites. Cell Growth Differ. 1990 Oct;1(10):503–510. [PubMed] [Google Scholar]
  18. SQUARTINI F., ROSSI G., PAOLETTI I. Characters of mammary tumours in BALB/c female mice foster-nursed by C3H and RIII mothers. Nature. 1963 Feb 2;197:505–506. doi: 10.1038/197505a0. [DOI] [PubMed] [Google Scholar]
  19. Shackleford G. M., Varmus H. E. Expression of the proto-oncogene int-1 is restricted to postmeiotic male germ cells and the neural tube of mid-gestational embryos. Cell. 1987 Jul 3;50(1):89–95. doi: 10.1016/0092-8674(87)90665-9. [DOI] [PubMed] [Google Scholar]
  20. Thomas K. R., Capecchi M. R. Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature. 1990 Aug 30;346(6287):847–850. doi: 10.1038/346847a0. [DOI] [PubMed] [Google Scholar]
  21. Tsukamoto A. S., Grosschedl R., Guzman R. C., Parslow T., Varmus H. E. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell. 1988 Nov 18;55(4):619–625. doi: 10.1016/0092-8674(88)90220-6. [DOI] [PubMed] [Google Scholar]
  22. Van Nie R., Verstraeten A. A., De Moes J. Genetic transmission of mammary tumour virus by GR mice. Int J Cancer. 1977 Mar 15;19(3):383–390. doi: 10.1002/ijc.2910190316. [DOI] [PubMed] [Google Scholar]
  23. Wilkinson D. G., Peters G., Dickson C., McMahon A. P. Expression of the FGF-related proto-oncogene int-2 during gastrulation and neurulation in the mouse. EMBO J. 1988 Mar;7(3):691–695. doi: 10.1002/j.1460-2075.1988.tb02864.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. van Nie R., Verstraeten A. A. Studies of genetic transmission of mammary tumour virus by C3Hf mice. Int J Cancer. 1975 Dec 15;16(6):922–931. doi: 10.1002/ijc.2910160606. [DOI] [PubMed] [Google Scholar]

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