Molecular Probes for an Oncogene Regulatory Protein

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 ofnormal breast epithelial cells to a cancerous phenotype. In reality, more than one-half of breast cancersare associated with high expression of ERBB2. We will develop molecular probes for a protein thatbinds to the ERBB2 promoter and may regulate ERBB2 gene expression leading to the development andprogression of breast cancer. A DNA binding protein that specifically binds to the promoter region ofthe ERBB2 gene has been detected at high concentrations in samples of adenocarcinoma admixed withcarcinoma of the breast, and is almost undetectable in adjacent benign breast tissue. These preliminaryresults 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 preneoplasticepithelial cells to carcinoma and a metastatic phenotype. Therefore, antibodies and nucleic acid probesspecific for ERP should have widespread applications for staging of human breast biopsy specimens andmay prove useful for determining and monitoring chemotherapeutic treatment protocols.