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

Abstract

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.

• Authors: Pei He, Dan Zhu, Jun-Jian Hu, Ju Peng, Lian-Sheng Chen, Guang-Xiu Lu
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 37 Issue 3 Pg. 1597-604 (Mar 2010) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 19444644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• MAS1 protein, human
• Proto-Oncogene Mas
• RNA, Catalytic
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adenocarcinoma (therapy)
• Animals
• Blotting, Western
• Breast Neoplasms (therapy)
• Cell Line, Tumor
• DNA Primers (genetics)
• Female
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (genetics)
• Gene Targeting (methods)
• Genetic Therapy (methods)
• Genetic Vectors (genetics)
• Humans
• Mice
• Mice, Nude
• Proto-Oncogene Mas
• RNA, Catalytic (genetics, pharmacology)
• Receptor, ErbB-2 (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection