The Role of Estrogen Receptor alpha K303R Mutation in Breast Cancer Metastasis
Abstract
The activity of estrogen receptor a is activated by both ligand binding and various modifications including phosphorylation and acetylation. Recently we have isolated a somatic ERalpha mutation which occurs in the major p300 acetylation site of ERalpha(Lys 303 to Arg, K303R)in human breast hyperplasias. This mutant is significantly correlated with both breast tumorigenesis and development. We report here that a component of the nucleosome remodeling and histone deacetylase complexes (NuRD), called metastasis-associated protein 1-like 1 (MTA1-L1),is an ERalpha binding protein both in vivo and in vitro. Also, we found that this interaction is ligand independent and requires the N-terminal region of MTA1-L1 and multiple domains of ER, Furthermore, we show that MTA1-L1 downregulates wild-type ERalpha, but not the K303R ERalpha mutation activities in transient transactivation assays. Taken together, our results suggest that the alterated ERalpha-containing NuRD function due to the K303R mutation could be a possible mechanism for this hypersensitive phenomenon.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417835
Entities
People
- Suzanne A. Fuqua
- Yukun Cui
Organizations
- Baylor College of Medicine