The long term objective of this project is to understand the regulation of mouse mammary tumor virus (MMTV) expression in normal mammary epithelium and how this control translates into the increased incidence of mammary tumorigenesis in nonpregnant, non-lactating parous mice vs. virgin mice. Until now MMTV expression has been best characterized in tumor or transformed cell lines. Unfortunately, there exists discrepancies between the results from these studies and those performed in normal mammary epithelium with respect to both the induction kinetics and hormonal requirements. Because the earlier studies involving normal mammary epithelium are both few and also employ indirect assays, it is the purpose of this project to re- evaluate and extend these investigations using DNA excess hybrization to measure MMTV RNA and radioimmunoassays to measure MMTV peptides. the working hypothesis is derived from a model originally proposed by others: MMTV expression is tightly controlled in virgins and is evoked during pregnancy by elevated hormone levels; this expression then alters the mammary epithelium so that MMTV expression can either continue after pregnancy or, at least, be more readily inducible. The final result is that MMTV expression is less rigidly regulated in parous vs. virgin mice. In particular, it is predicted that MMTV expression in mammary epithelium from parous mice will not require DNA synthesis prior to expression (DNA synthesis is required in tissues from virgins), will require fewer hormones or lesser concentrations of hormones and will be more sensitive to other MMTV inducers and/or less susceptible to MMTV inhibitors than in tissues from virgins. These experiments will be carried out in mammary explant culture in serum-free medium. This project is related to biomedical research in several ways: 1) it will provide more relevant information on the control of MMTV expression in the normal mouse mammary gland, and 2) it may provide insights into the etiology of at least some human breast cancers; which have recently been shown to contain MMTV-like sequences.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA042009-01A2
Application #
3182723
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1987-08-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
1
Fiscal Year
1987
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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