A Novel Repressor of Estrogen-Regulated Genes for Breast Cancer Growth Suppression
Abstract
The objective of this project is to develop and use novel ER mutants to test a two-part hypothesis. First, that the estrogen-independent growth of breast cancer cells involves the estrogen-independent expression of growth control genes which are normally estrogen regulated. Second, that suppressing the expression of these genes will block the growth of breast cancer cells. To test these ideas, we set out to develop a novel type of estrogen receptor chimera which will efficiently and quantitatively suppress both estrogen-dependent and estrogen/independent expression of estrogen-regulated growth stimulatory genes. To develop Estrogen Regulated Gene repressors (ERG-repressors), we constructed plasmids encoding a variety of recombinant estrogen receptors fused to different versions of the KRAB repressor domain. Another class of repressors was constructed by fusing the KRAB repressor domain to mutant DNA binding domains selected with the P22 challenge phage system, displaying a strongly enhanced affinity for the estrogen response element (ERE). The activity of these chimeric proteins as ERG-repressors was has evaluated in transient transfection assays and KRAB-estrogen receptor chimeras which are potent gene repressors have been identified.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADB244278
Entities
People
- David J. Shapiro
Organizations
- University of Illinois Urbana–Champaign