Membrane Estrogen Receptor Alpha Targeting and Its Association With SHC in Regulating Breast Cancer Cell Proliferation
Abstract
17BETA-ESTRADIOL (E2) induces rapid, non-genomic effect in MCF-7 breast cancer cells, including rapid activation of MAPK, phosphorylation of adapter protein Shc, increase of the interaction between Shc and estrogen receptor (ERalpha). More strikingly E2 also induced a rapid membrane association of ERalpha: (1) Further studying the structure and function of ERalpha, we demonstrated that only membrane-associated ERalpha, but not cytosol and nuclear ones, mediates E2 effect on MAPK activation. (2) To study the mechanism of ERalpha membrane association, we further investigated the role of Shc in estrogen action. Here we demonstrated that in MCF-7 cells, Shc acts as a chaperon linking ERalpha to the cell membrane by binding to a transmembrane receptor IGF-1R. Further study is under the way to investigate the molecular mechanism among these protein complex formation and their biological effects in estrogen non-genomic action.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417786
Entities
People
- Robert X-d. Song
Organizations
- University of Virginia