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.
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