Targeting RhoC by Way of Ribozyme Trangene?in Human Breast Cancer Cells and its Impact on Cancer Invasion

摘要

Background: Cell motility and migration are known to be regulated by the Rho family of GTPases through their effects on the actin cytoskeleton. In breast cancer studies, RhoC has been identified as a highly specific marker in detecting tumors that developed metastases. This study aims to investigate the impact of targeting RhoC in human breast cancer cells by utilising ribozyme transgene technology and to assess its effect on cancer cell invasion.Methods: Retroviral hammerhead ribozyme transgenes, regulated by doxycycline, were designed to specifically target human RhoC mRNA. The breast cancer cell line MDA-MB-231 was transfected with either a retroviral RhoC transgene or a control retroviral transgene. Stably transfected cells were tested for their invasiveness and migratory properties in vitro. Results: In vitro testing of the invasiveness of wild type, plasmid control and the RhoC knockdown cells showed that MDA-MB-231DRHOC cells had significantly reduced invasiveness compared with MDA-MB-231WT (p 0.1 for all three ribozymes). Conclusions: This data would indicate that targeting RhoC may be an effective way to reduce the invasive potential of human breast cancer cells.doi:10.4021/wjon2010.01.1202