Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells

Abstract

HER-2/neu is overexpressed in 25-30% of human breast cancers. We prepared an anti-HER-2/neu hammerhead ribozyme expressed by a recombinant adenovirus (rAdHER-Rz). Human breast cancer cell lines were transduced with high efficiency, resulting in decreased HER-2/neu expression. In vivo injections of rAdHER-Rz into BT-474 tumors established in nude mice inhibited tumor growth to 20% of mock-treated controls. Similar in vivo effects were shown in MCF-7 cells, which do not overexpress HER2/neu. The growth inhibitory effects of rAdHER-Rz were greater than those of an antisense-expressing vector These results suggest the utility of anti-HER-2/neu ribozymes as a rational strategy for gene therapy of breast cancer.