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

HER-2/neu is overexpressed in 25-30% of human breast cancers. We prepared a n anti-HER-2/neu hammerhead ribozyme expressed by a recombinant adenovirus (rAdHER-Rz). Human breast cancer cell lines were transduced with high effic iency, resulting in decreased HER-2/neu expression. In vivo injections of r AdHER-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 HER-2/neu. The growth inhibitory effects of rAdHER-Rz were greater than those of an antisense-expressing vector. Th ese results suggest the utility of anti-HER-2/neu ribozymes as a rational s trategy for gene therapy of breast cancer.