Targeting HER-2/neu Overexpression by Suicide Ribozyme in Breast Cancer
Abstract
Breast cancer represents a major cause of death for women in the United States. Overexpression of HER- 2/neu oncogene was found in approximately 30% of breast tumor tissues and shown to be a marker indicating poor prognosis for breast cancer patients. HER-2/neu overexpression in cancer cells is also known to enhance cancer metastasis and to induce chemoresistance to certain anti-cancer drugs and repression of HER-2/neu expression reduces malignancy of the cancer cells. Therefore, HER-2/neu overexpression serves as an excellent target for development of breast cancer therapy. Ribozymes have been successfully used to control gene expression. We have designed a novel suicide ribozyme that will allow a gene of interest (such as a toxin gene) to be expressed specifically in the HER-2/neu- overexpressing breast cancer cells, and therefore, will kill only the HER-2/neu-overexpressing cells. This report describes the progress in the following specific aims: I) Design of the suicide ribozyme and proof of concept in vitro; 2) Proof of concept in vivo: a reporter gene regulated by the suicide ribozyme will be expressed only in cells overexpressing HER-2/neu mRNA. 3) Application of concept in vivo: a toxin gene regulated by the suicide ribozyme will preferentially inhibit the growth of breast cancer cells that overexpress HER-2/neu.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA338914
Entities
People
- Mien-Chie Hung
Organizations
- The University of Texas MD Anderson Cancer Center