The objective of the experiments described in this proposal is to dissect the molecular mechanisms which affect the developmental regulation of expression of the endogenous murine retrovirus, mouse mammary tumor Virus (MTV) and limit the induction of mammary carcinomas by this virus to the mammary gland. An additional goal is to achieve an understanding of the genetic factors that determine whether mice are susceptible to MTV-induced mammary tumors and the role of the immune system in this process. To achieve these goals, a combination of molecular cloning techniques, tissue culture transfection studies and transgenic mice will be used to characterize the DNA sequences within the long terminal repeat (LTR) of MTV that direct expression of the virus to the mammary gland. Additionally, the transcription factors that Interact with these DNA sequences will be cloned and used to study expression of these factors in the developing mammary gland of different mouse strains and in mammary tumors. Lastly, the role of the MTV LTR open reading frame (ORF) protein, which influences the T cell repertoire in mice, will be assessed, In both the virus life cycle and in the susceptibility of different strains of mice to MTV-induced carcinomas. The experiments outlined in this proposal will allow us to begin to dissect the contributions of genetic background to the tumorigenic process initiated by MTV and the role of the immune system in responding to viral infection and tumorigenesis. By extension, these experiments will also increase our understanding of the role of these different components in human breast cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Illinois at Chicago
Schools of Medicine
United States
Zip Code
Okeoma, Chioma M; Shen, Ming; Ross, Susan R (2008) A novel block to mouse mammary tumor virus infection of lymphocytes in B10.BR mice. J Virol 82:1314-22
Courreges, Maria Cecilia; Burzyn, Dalia; Nepomnaschy, Irene et al. (2007) Critical role of dendritic cells in mouse mammary tumor virus in vivo infection. J Virol 81:3769-77
Burzyn, Dalia; Rassa, John C; Kim, David et al. (2004) Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus. J Virol 78:576-84
Rassa, John C; Ross, Susan R (2003) Viruses and Toll-like receptors. Microbes Infect 5:961-8
Czarneski, Jennifer; Rassa, John C; Ross, Susan R (2003) Mouse mammary tumor virus and the immune system. Immunol Res 27:469-80
Lee, James C; Kim, David C; Gee, Michael S et al. (2002) Interleukin-12 inhibits angiogenesis and growth of transplanted but not in situ mouse mammary tumor virus-induced mammary carcinomas. Cancer Res 62:747-55
Rassa, John C; Meyers, Jennifer L; Zhang, Yuanming et al. (2002) Murine retroviruses activate B cells via interaction with toll-like receptor 4. Proc Natl Acad Sci U S A 99:2281-6
Czarneski, Jennifer; Berguer, Paula; Bekinschtein, Pedro et al. (2002) Neonatal infection with a milk-borne virus is independent of beta7 integrin- and L-selectin-expressing lymphocytes. Eur J Immunol 32:945-56
Czarneski, J; Meyers, J; Peng, T et al. (2001) Interleukin-4 up-regulates mouse mammary tumor virus expression yet is not required for in vivo virus spread. J Virol 75:11886-90
Hook, L M; Agafonova, Y; Ross, S R et al. (2000) Genetics of mouse mammary tumor virus-induced mammary tumors: linkage of tumor induction to the gag gene. J Virol 74:8876-83

Showing the most recent 10 out of 28 publications