Targeting Human Breast Cancer Cells That Overexpress HER-2/neu mRNA by an Antisense Iron Responsive Element
Abstract
In this project, we attempt to establish the utility of an antisense iron-responsive element (AS-IRE)-mediated gene expression system to targeting HER-2/neu-overexpressing breast cancer cells. During the first two years of funding, we have finished the proposed goal stated in Task 1 by identifying the optimal HER-2/neu antisense IRE, i.e., AS-IRE4. Moreover, we showed preferential cell killing in HER-2/neu-overexpressing MDA-MB-453 cells using hTERT-AS-IRE4-Bax as opposed to in low HER-2/neu-expressing MDA-MB-468 cells (Task 2). The results obtained from Task 1 and 2 have been published in Cancer Letters (174:151-158, 2001). To test the therapeutic efficacy of the hTERT-AS-IRE4-luc in a pre-clinical gene therapy model (Task 3), our next goal is to use a binary adenoviral vector Bax gene expression system to test the preferential killing of HER-2-overexpressing breast cancer cells in vitro and in vivo. To demonstrate the feasibility of adenovirus-based gene therapy in our orthotopic breast cancer xenograft model, we showed that adenoviral vector-mediated therapeutic gene transfer could yield treatment efficacy as indicated by our recent publication in Clinical Cancer Research (8:3290-3297, 2002). In addition, we have staffed to explore the possibility of using small interference RNA (SiRNA) as a novel approach to specific target HER-2-overexpressing cells. Our preliminary results suggested that SiRNA is potentially a powerful technology to achieve specific downregulation of HER-2/neu gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA413974
Entities
People
- Duen-hwa Yan
Organizations
- The University of Texas MD Anderson Cancer Center