Ribozyme Targeting of Steroid Receptor Co-Activators: A Therapeutic Approach to Breast Cancer
Abstract
The gene of the nuclear receptor co activator AIB 1 is amplified in breast cancer cell lines as well as in breast tumor tissue. AIB 1 mRNA is often highly expressed in primary breast tumors and is has been shown that AIB 1 enhances estrogen and progesterone dependent transcription in vitro. Therefore it has been postulated that AIB 1 contributes to the development of breast cancer. However, it is currently not known what the precise role of AIB 1 is in the development of breast cancer. Our strategy to address this question is to establish breast cancer cell lines in which we can regulate AIB 1 levels with ribozymes in order to determine the impact of reduced AIB 1 gene expression on the phenotype and angiogenic or invasive properties of breast cancer cells. During the first year we developed MCF-7 breast cancer cells in which we are able to downregulate AIB 1 protein levels by up to 90%. Furthermore, downregulation of AIB 1 levels reduced the ability of the progesterone receptor to fully activate a progesterone regulated test promoter. We anticipate that our study will give valuable insights into the biological significance of AIB 1 as well as its potential role as a therapeutic target in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA387789
Entities
People
- Anna T. Riegel
Organizations
- Georgetown University