A Unique Breast Cancer Cell Model for Studying Reported Functions of Membrane-Localized Estrogen Receptor
Abstract
We previously developed a cell line system in which exogenous expression of estrogen receptor alpha (ERalpha) in an ERalpha-negative cell line resulted in ERalpha -mediated signaling and proliferation. We have now generated cell lines that express ERalpha only in the cytoplasm (cERalpha) to characterize the putative cytoplasmic (non-genomic) function of ERalpha. We have found that the cERalpha can bind estrogen and is down-regulated, similar to wild-type ERalpha. Intriguingly, the cERalpha is completely resistant to 1C118278O-mediated degradation. cERalpha can't activate gene transcription (due to its inability to enter the nucleus), and also can't stimulate cell cycle progression. Consistent with the cERalpha not activating gene transcription or cell cycle progression, cERalpha is not able to induce ER-regulated genes. Despite evidence that in some systems that estrogen can have short-term rapid signaling events, we do not find that expression of cERalpha increases short-term signaling in C4-12 cells. We are currently using a rhodopsin-tagged ER which is in the plasma membrane to determine if membrane association is critical for short-term signaling, and also whether cERalpha can increase short-term estrogen signaling in MCF-7 cells that overexpress HER2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425595
Entities
People
- Adrian V Lee
Organizations
- Baylor College of Medicine