The mouse mammary tumor virus (MMTV) is a retrovirus that causes mammary tumors in mice. During lactation, it is secreted into the milk which infects the pups; it also reinfects the dam's mammary epithelium, thereby increasing its chances of integrating near a protooncogene and producing transformation. Therefore, both the initial infection and reinfection are of primary importance in MMTV-induced tumorigenesis and they are both mediated by a cell surface receptor. It is the specific aim of this project to characterize the MMTV receptor with respect to physiochemical properties, histological localization, regulation and metabolism. The working hypotheses include the following: l) both MMTV receptor number and polarity will be related to the ability and route of tissue infection; 2) the mammary gland receptor will be closely related, if not identical, to the liver receptor; and 3) because these receptors probably serve an important role in mammary gland development and physiology, they will be widely distributed evolutionarily. To test these hypotheses, an in vitro infection system for MMTV has been developed in this laboratory and will be used to correlate receptor levels with infectivity. Receptor localization and metabolism will be studied by immunohistochemistry using antiserum developed against the liver MMTV binding protein. The mammary gland receptor will also be isolated, since viral receptors in different tissues may not be identical. These studies will be done with C3H mice (Mus); however, MMV binding activity has also been demonstrated on deer mouse (Peromyscus) epithelial cells. Therefore, this distant species will be used to investigate the nature and functionality of this receptor. This project is related to biomedical research in that it will give insights to how viruses can exploit plasma membrane proteins in order to initiate infec- tion. In particular, the MMTV system shares many important characteristics with several other oncoviruses closely related to human cancers, such as the human papilloma virus (cervical cancer), the human immunodeficiency virus (Kaposi's sarcoma) and the human T-cell leukemia virus. This may lead to better strategies for blocking these viruses at the point of infection.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA042009-07
Application #
3182725
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1987-08-01
Project End
1996-09-29
Budget Start
1993-09-30
Budget End
1994-09-29
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Type
Schools of Arts and Sciences
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
Bolander Jr, F F (1998) Regulation of mammary hormone receptor metabolism by a retroviral envelope protein. J Mol Endocrinol 21:161-8
Bolander Jr, F F; Ginsburg, E; Vonderhaar, B K (1997) The regulation of mammary prolactin receptor metabolism by a retroviral envelope protein. J Mol Endocrinol 19:131-6
Bolander Jr, F F (1997) Second messengers induced by the envelope protein of a retrovirus. Mol Cell Endocrinol 129:27-32
Bolander Jr, F F (1996) Requirements for mouse mammary tumour virus internalization in mouse mammary epithelial cells. J Gen Virol 77 ( Pt 4):793-6
Bolander Jr, F F (1994) The effect of mouse mammary tumor virus receptor activation on mammary epithelial cell sensitivity toward prolactin. Biochem Biophys Res Commun 205:524-8
Bolander Jr, F F (1994) Regulation of the mouse mammary tumor virus receptor by phosphorylation and internalization in mammary epithelial cells. J Cell Physiol 161:124-8
Bolander, F F; Blackstone, M E (1991) Tissue distribution of the cellular binding protein for the mouse mammary tumour virus. J Mol Endocrinol 7:169-74
Bolander Jr, F F (1991) Regulation of the mouse mammary tumor virus (MMTV) binding site in cultured mammary tissue. Mol Cell Endocrinol 82:137-42
Bolander, F F; Blackstone, M E (1990) Developmental and hormonal regulation of a mouse mammary tumour virus glycoprotein in normal mouse mammary epithelium. J Mol Endocrinol 4:101-6
Bolander Jr, F F; Blackstone, M E (1990) Thyroid hormone requirement for retinoic acid induction of mouse mammary tumor virus expression. J Virol 64:5192-3

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