Estrogen Receptor-Mediated Transcription In Vitro
Abstract
Estrogen receptor (ER) is a ligand activated transcription activator. The detailed mechanism of ER mediated transcription is unclear. We demonstrated that ER mediated transcription in cell free transcription system is ligand dependent. Antiestrogens ICI 164,384, ICI 182,780 and 4-hydroxytamoxifen significantly inhibited ER mediated transcription. Estradiol overcame the inhibitory effect of the antiestrogens and induced ER mediated transcription. Under the condition used for the transcription assay, ICI164,384 and ICI182,780 inhibited ER-ERE complex formation which might contribute to the inhibitory effect of these antiestrogens on ER mediated transcription. 4 OH TAM changed the mobility of ER ERE complex which suggests a conformational change of the complex. Steroid receptor coactivator 1 (SRC- 1) significantly augmented ER mediated transcription in vitro, supporting that SRC-1 is involved in ER signal pathway. ER hormone binding domain (HBD) that binds to ER associated proteins (ERAPs) in a ligand dependent manner in previously studies inhibited ER mediated transcription in vitro. In contrast, truncated ER HED lacking of 535 to 595 amino acids which binds to estradiol but does not associate with ERAPs did not affect ER Mediated effect in this study, suggesting that ERAPs are required for the full transactivation activity of ER.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1997
- Accession Number
- ADA340593
Entities
People
- Hong Liu
- Myles A. Brown
Organizations
- Dana–Farber Cancer Institute