Role of Estrogen Receptor Target Genes in Breast Cancer
Abstract
Estrogen receptor (ER) is ligand-dependent transcription factor that has an important role in the development and progression of breast cancer. In this study, we developed a chimeric repressor to turn off ER target genes with the aim to directly investigate the role of ER target genes in tumor progression. The chimeric repressor contains the ER DNA-binding domain, a Krupple-Associated Box (KRAB) repressor domain and a truncated progesterone ligand-binding domain. The ability of the chimeric repressor to block ER mediated transcription was assessed in transient transfection assays. ER-induced reporter activity was inhibited by the repressor in a dose-dependent manner, with the maximum effect of more than 80% reduction. The inhibitory activity of the chimeric repressor was tightly under the control of RU486. Though we successfully generated regulable repressors to inhibit the ER reporter genes in vitro in transient transfection, these repressors fail to suppress endogenous ER target gene expression in breast cancer cell lines. More efforts need to be focus on in vivo gene expression. The success in creating such a repressor will provide a useful tool to study the role of ER target genes in breast cancer progression, and it may be potentially useful for gene therapy of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2001
- Accession Number
- ADA391930
Entities
People
- Sophia Y. Tsai
- Zhi-qing Ma
Organizations
- Baylor College of Medicine