title: A vector-based short hairpin RNA targeting Aurora A inhibits breast cancer growth.
abstract: Aurora A plays an essential role in centrosome maturation, separation and in the formation of the mitotic bipolar spindle. Overexpression or amplication of Aurora A gene has been detected in many cancer cell lines and various tumor tissues, including breast cancer, suggesting that Aurora A might be drug target for breast cancer treatment. In the current study, short hairpin RNA targeting Aurora A was cloned into pGenesil-2 plasmid vector and then transfected into MDA-MB-435S and ZR-75-30 human breast cancer cells using cationic liposome. Reduced expression of Aurora A was detected by RT-PCR and Western blot. The effect of pGenesil-2-shAURKA plasmid on tumor growth in MDA-MB-435S xenogenic implantation model was studied. pGenesil-2-shAURKA plasmid inhibited tumor growth significantly by systemantic administration. To further study the underlying mechanisms, cell apoptosis and proliferation were investigated by flow cytometric analysis, propidium iodide staining, TUNEL and Ki-67 immunostaining respectively. Increased apoptosis and reduced cell proliferation were detected in vitro and in vivo studies. In summary, our results suggested that specific knockdown of Aurora A expression by vector based shRNA may be a potential therapy for human breast cancer.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital and West China Medical School, Sichuan University, Sichuan, 610041, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.forename: Anliang
authors.initials: A
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Gang
authors.initials: G
authors.lastname: Xie
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Xiancheng
authors.initials: X
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Hongxin
authors.initials: H
authors.lastname: Deng
mesh_terms: D064127:Aurora Kinases; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002412:Cations; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005821:Genetic Techniques; D005822:Genetic Vectors; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008081:Liposomes / Q000737:chemistry; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002412:Cations; D019394:Ki-67 Antigen; D008081:Liposomes; D004247:DNA; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases