Breast cancer is a complex disease requiring multidimensional approaches to elucidate causative processes. Our overall goal is to define molecular and cellular mechanisms important in mammary tumorigenesis, utilizing the BALB/c mouse model and known etiologic factors, virus (MMTV) and chemical carcinogen (DMBA). This system provides an unparalleled opportunity to assess molecular changes underlying discrete stages of breast carcinogenesis. Our hypothesis is that the MMTV long terminal repeat (LTR) superantigen gene product [pORF(sag)] is multifunctional in the viral life cycle and in mammary tumorigenesis.
Specific aims are the following: (1) To characterize LTR pORFsag) expressed in murine cells. (2) To identify LTR pORF interactive cellular proteins using the yeast two-hybrid system. (3) To investigate the role of mammary oncogenes in DMBA-induced mammary tumorigenesis. Identification and functional analysis of pORF(sag) interactive cellular proteins will reveal regulatory processes important in mammary cell growth and development. This analysis will also provide basic information about the prototype viral superantigen [pORF(sag)]. This program builds on our experience with the mammary tumor system, viral oncoprotein-cell regulatory protein interactions, and endogenous MMTV expression in normal and DMBA-transformed mammary cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA033369-14
Application #
2007383
Study Section
Chemical Pathology Study Section (CPA)
Program Officer
Okano, Paul
Project Start
1982-09-01
Project End
1998-12-31
Budget Start
1997-01-01
Budget End
1998-12-31
Support Year
14
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Mukhopadhyay, R; Medina, D; Butel, J S (1995) Expression of the mouse mammary tumor virus long terminal repeat open reading frame promotes tumorigenic potential of hyperplastic mouse mammary epithelial cells. Virology 211:74-93
Lopez-Cepero, M; Wang, Y; Keydar, I et al. (1995) Detection of retroviral superantigen and products of the envelope gene from endogenous mouse mammary tumor virus in B cells from BALB/c mice. Cell Immunol 163:191-7
Jerry, D J; Medina, D; Butel, J S (1994) p53 mutations in COMMA-D cells. In Vitro Cell Dev Biol Anim 30A:87-9
Jerry, D J; Butel, J S; Donehower, L A et al. (1994) Infrequent p53 mutations in 7,12-dimethylbenz[a]anthracene-induced mammary tumors in BALB/c and p53 hemizygous mice. Mol Carcinog 9:175-83
Brandt-Carlson, C; Butel, J S; Wheeler, D (1993) Phylogenetic and structural analyses of MMTV LTR ORF sequences of exogenous and endogenous origins. Virology 193:171-85
Kittrell, F S; Oborn, C J; Medina, D (1992) Development of mammary preneoplasias in vivo from mouse mammary epithelial cell lines in vitro. Cancer Res 52:1924-32
Brandt-Carlson, C; Butel, J S (1991) Detection and characterization of a glycoprotein encoded by the mouse mammary tumor virus long terminal repeat gene. J Virol 65:6051-60
Durban, E M; Knepper, J E; Medina, D et al. (1990) Influence of mammary cell differentiation on the expression of proteins encoded by endogenous BALB/c mouse mammary tumor virus genes. Virus Res 16:307-23
Kumar, R; Medina, D; Sukumar, S (1990) Activation of H-ras oncogenes in preneoplastic mouse mammary tissues. Oncogene 5:1271-7
Knepper, J E; Kittrell, F S; Medina, D et al. (1989) Spontaneous progression of hyperplastic outgrowths of the D1 lineage to mammary tumors: expression of mouse mammary tumor virus and cellular proto-oncogenes. Mol Carcinog 1:229-38

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