MMTV Infectious Cycle and the Contribution of Virus-encoded Proteins to Transformation of Mammary Tissue

Department of Microbiology/Abramson Family Cancer Center, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA 1914, USA.
Journal of Mammary Gland Biology and Neoplasia (Impact Factor: 5). 09/2008; 13(3):299-307. DOI: 10.1007/s10911-008-9090-8
Source: PubMed

ABSTRACT Mouse mammary tumor virus has served as a major model for the study of breast cancer since its discovery 1920's as a milk-transmitted agent. Much is known about in vivo infection by this virus, which initially occurs in lymphocytes that then carry virus to mammary tissue. In addition to the virion proteins, MMTV encodes a number of accessory proteins that facilitate high level in vivo infection. High level infection of lymphoid and mammary epithelial cells ensures efficient passage of virus to the next generation. Since MMTV causes mammary tumors by insertional activation of oncogenes, which is thought to be a stochastic process, mammary epithelial cell transformation is a by-product of the infectious cycle. The envelope protein may also participate in transformation. Although there have been several reports of a similar virus in human breast cancer, the existence of a human MTV has not been definitely established.

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    • "The transforming qualities of retroviruses have been appreciated for over a century [1]. Although the specific nature of mechanisms involved in retroviral infection was not appreciated until 1970 with the identification of reverse transcriptase, they had already been implicated in the initiation and promotion of many cancers in animals [1] [2]. Their role in human cancers has only begun to be appreciated in more recent years. "
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    ABSTRACT: Retroviral transformation has been associated with pro-proliferative oncogenic signaling in human cells. The current study demonstrates that transduction of human breast carcinoma cells (MDA-MB231) with LXSN and QCXIP retroviral vectors causes significant increases in growth rate, clonogenic fraction, and aldehyde dehydrogenase-1 positive cells (ALDH1+), which is associated with increased steady-state levels of cancer stem cell populations. Furthermore, this retroviral-induced enhancement of cancer cell growth in vitro was also accompanied by a significant increase in xenograft tumor growth rate in vivo. The retroviral induced increases in cancer cell growth rate were partially inhibited by treatment with 100 U/ml polyethylene glycol-conjugated-(PEG)-superoxide dismutase and/or PEG-catalase. These results show that retroviral infection of MDA-MB231 human breast cancer cells is capable of enhancing cell proliferation and cancer stem cell populations as well as suggesting that modulation of reactive oxygen species-induced pro-survival signaling pathways may be involved in these effects.
    06/2014; 2. DOI:10.1016/j.redox.2014.06.006
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    • "The infected lymphocytes traffic to the mammary gland, resulting in the infection of mammary epithelial cells (MECs) during puberty and pregnancy. Lactating mice shed high levels of cell-free virus into milk, which is then acquired by nursing offspring during the 1 st week of life (Ross, 2008). "
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    ABSTRACT: Viruses, including retroviruses like human immunodeficiency virus (HIV) and mouse mammary tumor virus (MMTV), are transmitted from mother to infants through milk. Lymphoid cells and antibodies are thought to provide mammary gland and milk-borne immunity. In contrast, little is known about the role of mammary epithelial cells (MECs). The APOBEC3 family of retroviral restriction factors is highly expressed in macrophages and lymphoid and dendritic cells. We now show that APOBEC3 proteins are also expressed in mouse and human MECs. Lymphoid cell-expressed APOBEC3 restricts in vivo spread of MMTV to lymphoid and mammary tissue. In contrast, mammary gland-expressed APOBEC3 is packaged into MMTV virions and decreases the infectivity of milk-borne viruses. Moreover, APOBEC3G and other APOBEC3 genes are expressed in human mammary cells and have the potential to restrict viruses produced in this cell type. These data point to a role for APOBEC3 proteins in limiting infectivity of milk-transmitted viruses.
    Cell host & microbe 12/2010; 8(6):534-43. DOI:10.1016/j.chom.2010.11.003 · 12.19 Impact Factor
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