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.
He
Pei
P
Institute of Reproduction and Stem Cell Engineering, Central South University, National Center of Human Stem Cell Research and Engineering, Hunan, China.
Zhu
Dan
D
Hu
Jun-Jian
JJ
Peng
Ju
J
Chen
Lian-Sheng
LS
Lu
Guang-Xiu
GX
D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D000090063:Proto-Oncogene Mas; D016337:RNA, Catalytic / Q000235:genetics / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D017931:DNA Primers; D000090063:Proto-Oncogene Mas; D016337:RNA, Catalytic; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human; C508053:ERBB2 protein, human