Mouse Mammary Tumor Virus Molecular Biology and Oncogenesis

Susan R Ross

doi:10.3390/v2092000

Abstract

Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious cancer-inducing agent in the 1930s, has been used since that time as an animal model for the study of human breast cancer. Like other complex retroviruses, MMTV encodes a number of accessory proteins that both facilitate infection and affect host immune response. In vivo, the virus predominantly infects lymphocytes and mammary epithelial cells. High level infection of mammary epithelial cells ensures efficient passage of virus to the next generation. It also results in mammary tumor induction, since the MMTV provirus integrates into the mammary epithelial cell genome during viral replication and activates cellular oncogene expression. Thus, mammary 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.

Highlights

Non-acute transforming retroviruses, which cause dysregulated expression of cellular oncogenes upon integration of the provirus into the host genome, have long been used to study both tumor development and progression in animal models [1]
Sags encoded by endogenous mammary tumor virus (MMTV) cause the deletion of cognate T cells during shaping of the immune repertoire, while those encoded by exogenous virus produce a slower but none-the-less almost complete deletion of such lymphocytes [40]
The histopathological features of MMTV-induced tumors do not usually resemble the most frequent forms of human breast tumors such as invasive ductal carcinomas, many, if not all, of the human mammary lesions are thought to originate in the terminal ductal lobular unit and atypical lobular type A lesions (ALA) are morphologically similar to the mouse mammary hyperplastic alveolar nodule (HAN) lesions [51]

Summary

Introduction

Non-acute transforming retroviruses, which cause dysregulated expression of cellular oncogenes upon integration of the provirus into the host genome, have long been used to study both tumor development and progression in animal models [1]. Many oncogenes were originally identified because of their association with tumors caused by this type of retrovirus. The majority of Viruses 2010, 2 non-acute transforming retroviruses induce cancer in cells of hematopoietic origin, one exception is the murine betaretrovirus MMTV, which causes mammary epithelial cell tumors. Has long been used as an in vivo model for the study of human breast cancer [3]. I briefly review MMTV molecular biology, its in vivo infection pathway, and what has been learned about how this virus causes mammary tumors

MMTV genome and proteins

MMTV in vivo infection

MMTV and Mammary Tumorigenesis

Conclusions and perspectives