Anti-c-erb-B-2 Ribozyme for Breast Cancer

Our laboratory has investigated the cleavage activity of an-anti-c-erb -B-2 ribozyme. The c-erb -B-2 proto-oncogene (also called HER-2/neu ) encodes a 185 kDa transmembrane tyrosine kinase-type receptor that is homologous with the epidermal growth factor receptor (EGFR) (1 ,2 ) The putative ligand for c-erb -B-2 is thought to be gp30; however, its role in this process remains to be elucidated (3 ) Although EGFR can transform mouse NIH3T3 cells only in the presence of ligand and receptor (4 ), c-erb -B-2 overexpression can transform NIH3T3 cells in a ligand-independent manner (5 ,6 ). The c-erb -B-2 protein is constitutively phosphorylated and demonstrates tyrosine kinase activity without the presence of ligand when overexpressed in NIH3T3 cells (7 ) A possible role of c-erb -B-2 in human malignancy has been postulated, based on its identified amplification and overexpression in a variety of carcinomas (8 ). c-erb -B-2 overexpression may stimulate signal transduction pathways and lead to aberrant growth, resulting in the malignant phenotype. Human breast cancer has been shown to exhibit c-erb -B-2 overexpression in 20–30% of examined tumors (9 ,10 ). The prognostic significance of c-erb -B-2 overexpression in breast cancer has been investigated, and there appears to be a correlation between high levels of c-erb -B-2 expression and poor clinical outcome, particularly in patients with positive axillary lymph nodes (11 ,12 ).