pcDNA3.1(−)-mediated ribozyme targeting of HER-2 suppresses breast cancer tumor growth

The HER-2 proto-oncogene (also called c-erbB-2/neu) encodes the protein, p185, which is closely related to the growth and metastasis of adenocarcinoma, and is overexpressed in 25–30% of human breast cancers. In this study, we attempt to reverse the malignant phenotype of the breast cancer cell line, MCF-7, using a HER-2 -specific hammerhead ribozyme. Two anti- HER-2 hammerhead ribozymes, RZ1 and RZ2, were synthesized, inserted separately into the nonviral eukaryotic expression vector, pcDNA3.1(−), and transfected into MCF-7 cells. Analyses showed that the HER-2 mRNA and p185, as well as oncogene k-ras were down-regulated remarkably in the ribozyme-transfected cells, while the onco-suppressor gene, p53 , was up-regulated. Furthermore, the tumorigenicity of the RZ1-stably transfected MCF-7 cells was decreased dramatically in nude mice. These results demonstrate that the use of anti- HER-2 ribozymes may be a beneficial strategy for gene therapy of breast cancer.