The development of cancer is a complex process that appears to involve multiple mechanisms. Recent studies indicate that the Her-2/neu (ERBB2) gene may be important in the transformation of normal breast epithelial cells to a cancerous phenotype.In reality, more than one-half of breast cancers are associated with high expression of ERBB2. The goal of this proposal is to develop molecular probes for a protein that binds to the ERBB2 promoter and may regulate ERBB2 gene expression leading to the development and progression of breast cancer. A DNA binding protein that specifically binds to the promoter region of the ERBB2 gene has been detected at high concentrations in samples of adenocarcinoma admixed with carcinoma of the breast, and is almost undetectable in adjacent benign breast tissue. These preliminary results suggest that this protein (hereinafter referred to as the ERBB2 regulatory protein, or """"""""ERP""""""""), specifically interacts with the ERBB2 promoter, and may promote transformation of preneoplastic epithelial cells to carcinoma and a metastatic phenotype. Therefore, antibodies and nucleic acid probes specific for ERP should have widespread applications for staging of human breast biopsy specimens and may prove useful for determining and monitoring chemotherapeutic treatment protocols.
