Lessons Learned from Mouse Mammary Tumor Virus in Animal Models
Jaquelin P Dudley1, Tatyana V Golovkina1, Susan R Ross1
1Jaquelin P. Dudley, PhD, is a professor in the Department of Molecular Biosciences, Center for Infectious Disease and Institute for Cellular and Molecular Biology at the University of Texas at Austin. Tatyana V. Golovkina, PhD, is a professor in the Department of Microbiology at the University of Chicago in Chicago, Illinois. Susan R. Ross, PhD, is a professor in the Department of Microbiology in the Perelman School of Medicine of the University of Pennsylvania in Philadelphia, Pennsylvania.
Abstract:
Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious, cancer-inducing agent in the 1930s, has been used as an animal model for the study of retroviral infection and transmission, antiviral immune responses, and breast cancer and lymphoma biology. The main target cells for MMTV infection in vivo are cells of the immune system and mammary epithelial cells. Although the host mounts an immune response to the virus, MMTV has evolved multiple means of evading this response. MMTV causes mammary tumors when the provirus integrates into the mammary epithelial and lymphoid cell genome during viral replication and thereby activates cellular oncogene expression. Thus, tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer.
Insights
Mouse mammary tumor virus (MMTV) causes cancer by integrating into host DNA, activating oncogenes. This retroviral model aids research into immune evasion, breast cancer, and lymphoma biology.
Area of Science:
- Retroviral biology
- Oncology
- Immunology
Background:
- Mouse mammary tumor virus (MMTV) is an infectious, milk-transmitted retrovirus discovered in the 1930s.
- MMTV serves as a key animal model for studying retroviral infections, immune responses, and the biology of breast cancer and lymphoma.
Purpose of the Study:
- To investigate the mechanisms of MMTV-induced oncogenesis.
- To understand MMTV's interaction with the host immune system.
- To identify oncogenes involved in MMTV-driven tumor development.
Main Methods:
- Analysis of MMTV integration sites within host cell genomes.
- Studying MMTV infection in target immune and mammary epithelial cells.
- Investigating host antiviral immune responses and viral evasion strategies.
Main Results:
- MMTV primarily infects immune cells and mammary epithelial cells.
- Viral replication and proviral integration into host DNA activate cellular oncogenes, leading to tumor formation.
- MMTV employs multiple strategies to evade host immune responses.
- MMTV integration site analysis has identified several critical oncogenes.
Conclusions:
- Mammary tumor induction by MMTV is a consequence of its replication cycle and subsequent oncogene activation.
- MMTV serves as a valuable model for discovering oncogenes relevant to human breast cancer.
- Understanding MMTV's pathogenesis offers insights into retroviral-induced cancers and immune evasion.
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