Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1979 Oct;76(10):5360–5364. doi: 10.1073/pnas.76.10.5360

Mouse mammary tumor virus genome expression in chemical carcinogen-induced mammary tumors in low- and high-tumor-incidence mouse strains

S Dusing-Swartz *, D Medina *, J S Butel †, S H Socher *,‡
PMCID: PMC413142  PMID: 228289

Abstract

Involvement of mouse mammary tumor virus (MMTV) in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis was investigated in low- (BALB/c) and high- (BALB/cfC3H) mammary-tumor-incidence mouse strains. Both strains contain endogenous MMTV integrated into the cellular genome. Additionally, BALB/cfC3H mice are infected with exogenous MMTV-S which is responsible for a higher incidence of mammary tumors in breeding females. Administration of DMBA to virgin mice of both strains resulted in a moderate frequency of mammary tumors within 40 wk after treatment. No differences were found in DMBA-induced tumor incidences at 18 wk (6% and 7%) or at 38 wk (29% and 36%) after treatment of BALB/c and BALB/cfC3H mice, respectively. Expression of MMTV in these tumors was examined by assaying for the presence of MMTV RNA by hybridization using MMTV-specific cDNA and by immunohistochemical staining utilizing antibodies against MMTV 52,000-dalton glycoprotein, gp52, and 28,000-dalton internal protein, p28. Of 16 BALB/c tumors assayed, 11 did not contain detectable levels of MMTV RNA and the remaining 5 tumors contained only low levels (0.0005-0.0010%) of viral RNA. Importantly, MMTV RNA was not detected in 5 of 27 BALB/cfC3H tumors. The other BALB/cfC3H tumors contained quantities of MMTV RNA ranging from 0.0006 to 0.4170%. Most BALB/cfC3H tumors with detectable levels of MMTV RNA also synthesized viral proteins gp52 and p28. Thus, expression of the complete MMTV genome is not requisite for maintenance of the tumor phenotype in DMBA-induced mammary tumors in either BALB/c or BALB/cfC3H virgin mice under 1 year of age.

Keywords: 7,12-dimethylbenz[a]anthracene; BALB/c; BALB/cfC3H; molecular hybridization; immunohistochemical staining

Full text

PDF
5360

Selected References

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

  1. Bentvelzen P., Daams J. H., Hageman P., Calafat J., Timmermans A. Interactions between viral and genetic factors in the origin of mammary tumors in mice. J Natl Cancer Inst. 1972 Apr;48(4):1089–1094. [PubMed] [Google Scholar]
  2. Bentvelzen P. Host-virus interactions in murine mammary carcinogenesis. Biochim Biophys Acta. 1974 Dec 31;355(3-4):236–259. doi: 10.1016/0304-419x(74)90012-2. [DOI] [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. Dudley J. P., Butel J. S., Socher S. H., Rosen J. M. Detection of mouse mammary tumor virus RNA in BALB/c tumor cell lines of nonviral etiologies. J Virol. 1978 Dec;28(3):743–752. doi: 10.1128/jvi.28.3.743-752.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Keydar I., Mesa-Tejada R., Ramanarayanan M., Ohno T., Fenoglio C., Hu R., Spiegelman S. Detection of viral proteins in mouse mammary tumors by immunoperoxidase staining of paraffin sections. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1524–1528. doi: 10.1073/pnas.75.3.1524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. McGrath C. M., Marineau E. J., Voyles B. A. Changes in MuMTV DNA and RNA levels in Balb/c mammary epithelial cells during malignant transformation by exogenous MuTV and by hormones. Virology. 1978 Jun 15;87(2):339–353. doi: 10.1016/0042-6822(78)90139-3. [DOI] [PubMed] [Google Scholar]
  7. Medina D., Warner M. R. Mammary tumorigenesis in chemical carcinogen-treated mice. IV. Induction of mammary ductal hyperplasias. J Natl Cancer Inst. 1976 Aug;57(2):331–337. doi: 10.1093/jnci/57.2.331. [DOI] [PubMed] [Google Scholar]
  8. Michalides R., Vlahakis G., Schlom J. A biochemical approach to the study of the transmission of mouse mammary tumor viruses in mouse strains RIII and C3H. Int J Cancer. 1976 Jul 15;18(1):105–115. doi: 10.1002/ijc.2910180114. [DOI] [PubMed] [Google Scholar]
  9. Michalides R., van Deemter L., Nusse R., Röpcke G., Boot L. Involvement of mouse mammary tumor virus in spontaneous and hormone-induced mammary tumors in low-mammary-tumor mouse strains. J Virol. 1978 Sep;27(3):551–559. doi: 10.1128/jvi.27.3.551-559.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Morris V. L., Medeiros E., Ringold G. M., Bishop J. M., Varmus H. E. Comparison of mouse mammary tumor virus-specific DNA in inbred, wild and Asian mice, and in tumors and normal organs from inbred mice. J Mol Biol. 1977 Jul;114(1):73–91. doi: 10.1016/0022-2836(77)90284-4. [DOI] [PubMed] [Google Scholar]
  11. Nolin J. M., Witorsch R. J. Detection of endogenous immunoreactive prolactin in rat mammary epithelial cells during lactation. Endocrinology. 1976 Oct;99(4):949–958. doi: 10.1210/endo-99-4-949. [DOI] [PubMed] [Google Scholar]
  12. Palmiter R. D. Ovalbumin messenger ribonucleic acid translation. Comparable rates of polypeptide initiation and elongation on ovalbumin and globin messenger ribonucleic acid in a rabbit reticulocyte lysate. J Biol Chem. 1973 Mar 25;248(6):2095–2106. [PubMed] [Google Scholar]
  13. Pauley R. J., Medina D., Socher S. H. Murine mammary tumor virus expression during mammary tumorigenesis in BALB/c mice. J Virol. 1979 Feb;29(2):483–493. doi: 10.1128/jvi.29.2.483-493.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pauley R. J., Rosen J. M., Socher S. H. Mammary tumour virus and casein gene transcription during mouse mammary development. Nature. 1978 Oct 5;275(5679):455–457. doi: 10.1038/275455a0. [DOI] [PubMed] [Google Scholar]
  15. Rosen J. M., Barker S. W. Quantitation of casein messenger ribonucleic acid sequences using a specific complementary DNA hybridization probe. Biochemistry. 1976 Nov 30;15(24):5272–5280. doi: 10.1021/bi00669a012. [DOI] [PubMed] [Google Scholar]
  16. Rosen J. M., Socher S. H. Detection of casein messenger RNA in hormone-dependent mammary cancer by molecular hybridisation. Nature. 1977 Sep 1;269(5623):83–86. doi: 10.1038/269083a0. [DOI] [PubMed] [Google Scholar]
  17. Smith G. H., Pauley R. J., Socher S. H., Medina D. Chemical carcinogenesis in C3H/StWi mice, a worthwhile experimental model for breast cancer. Cancer Res. 1978 Dec;38(12):4504–4509. [PubMed] [Google Scholar]
  18. Varmus H. E., Bishop J. M., Nowinski R. C., Sarker N. H. Mammary tumour virus specific nucleotide sequences in mouse DNA. Nat New Biol. 1972 Aug 9;238(84):189–191. doi: 10.1038/newbio238189a0. [DOI] [PubMed] [Google Scholar]
  19. Varmus H. E., Quintrell N., Medeiros E., Bishop J. M., Nowinski R. C., Sarkar N. H. Transcription of mouse mammary tumor virus genes in tissues from high and low tumor incidence mouse strains. J Mol Biol. 1973 Oct 5;79(4):663–679. doi: 10.1016/0022-2836(73)90070-3. [DOI] [PubMed] [Google Scholar]
  20. Young B. D., Harrison P. R., Gilmour R. S., Birnie G. D., Hell A., Humphries S., Paul J. Kinetic studies of gene frequency. II. Complexity of globin complementary DNA and its hybridization characteristics. J Mol Biol. 1974 Apr 25;84(4):555–568. doi: 10.1016/0022-2836(74)90116-8. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES