Targeting Human Breast Cancer Cells that Overexpress HER-2/neu mRNA by an Antisense Iron Responsive Element
Abstract
Amplification and overexpression of the HER-2/neu gene were found in 20-30% of patients with breast cancer, and is an indicator for poor prognosis of the disease. To target the breast cancer cells-overexpressing HER-2/neu mRNA, a novel approach was developed. We combine the antisense principle and the biochemical property of a translation regulator, an iron responsive element (IRE) to preferentially express therapeutic gene in HER-2/neu overexpressing breast cancer cells. Briefly, IRE, when placed 5 to a gene, functions as a negative translation regulator in that IRE interacts with iron-regulatory proteins (IRPs) and this protein-RNA complex blocks translation. One way to alleviate this translation inhibition is to prevent the IRE/IRP interaction by disrupting the IRE stem-loop structure via a sense-antisense hybrid. Thus, we designed a HER-2/neu antisense IRE (AS-IRE) that possesses the IRE consensus sequence and functions as a translation inhibitor. When placed 5 to a reporter gene, AS-IRE could direct the reporter gene expression in breast cancer cells that overexpress HER-2/neu mRNA, because the AS-IRE-mediated translation inhibition can be overcome by the overexpression of HER-2/neu mRNA. In this project, we attempt to demonstrate the utility of this novel approach in vitro and in vivo by specifically directing gene expression in HER-2/neu-overexpressing breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADA385375
Entities
People
- Duen-hwa Yan
Organizations
- The University of Texas MD Anderson Cancer Center