The Mouse as a Model for Mammary Tumorigenesis: History and Current Aspects

Excerpt

The mouse has been an important model to define and understand the physiology and development of the mammary gland as well as to define the genetic pathways that control these processes. The mouse mammary tumor virus (MMTV), originally called the “milk factor”, has been shown to be a causative agent for mammary tumorigenesis in mice. Studies of the biology of MMTV led to an understanding that the ultimate target for viral infection of the mammary gland are the self renewing stem or progenitor cells of the gland. Infection of these cells can lead to the development of preneoplastic lesions called hyperplastic alveolar nodules or ductal derived “plaques” From within either of these lesions pregnancy independent mammary tumors arise as well as subsequent pulmonary metastatic lesions. An understanding of the route within the mouse with which the virus is distributed and mechanisms by which MMTV subverts the immune system and reaches mammary epithelial cells has been a major focus research and has led to the discovery of a cell receptor for MMTV. MMTV is a biological carcinogen that acts as an insertional mutagen of stem or progenitor mammary epithelial cells. Recent high throughput analysis of MMTV induced mammary tumors for common integration sites (CIS) for the viral genome demonstrate that there is a “Core” family of genes that are activated independent of the mouse or virus strain. This Core family contains members of the Wnt/Fgf/Rspo gene families. Other high frequency CIS that are strain specific are …