A Unique Breast Cancer Cell Model for Studying Reported Functions of Membrane-Localized Estrogen Receptor
Abstract
We have generated ER-negative breast cancer cell lines (C4-12) that express ERalpha only in the cytoplasm (cERalpha - deletion of the nuclear localization sequence) to characterize the putative cytoplasmic functions of ERalpha. As expected, estrogen stimulation of C4-12-cERalpha didn't stimulate genomic ER activity. However, estrogen also failed to increase growth of these cells and didn't stimulate non-genomic ER signaling via ERK1/2 or Akt. Interestingly, however, we found that estradiol stimulated cERalpha was degraded by the proteasome (challenging the notion that transcription and degradation are linked), and also found that cERalpha was completely resistant to ICI182780-mediated degradation. We have generated C4-12 cells expressing ERalpha exclusively in the plasma membrane (chimeric protein of rhodopsin fused to full length ERalpha and including the NLS) and found that estrogen is able to rapidly activate ERK1/2 in these cells. Rho-ER is degraded by estrogen and ICI, directly implicating the NLS of ER in ICI-mediated degradation. These studies do not support a major role for cytoplasmic ER in non-genomic ER signaling, however they clearly illustrate significant differences between estrogen and ICI-mediated ERalpha degradation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA455276
Entities
People
- Adrian Lee
Organizations
- Baylor College of Medicine