A Unique Breast Cancer Cell Model for Studying Reported Functions of Membrane-Localized Estrogen Receptor Alpha
Annual rept. 1 Apr 2002-31 Mar 2003
BAYLOR COLL OF MEDICINE HOUSTON TX
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We have recently developed a cell line system in which exogenous expression of estrogen receptor alpha ERalpha in an ERalpha-negative cell line results in ERalpha-mediated signaling and proliferation. We proposed in this project to express ERalpha mutants and use this system to define ERalpha action in breast cancer. We have generated breast cancer cells lines that express ERalpha only in the cytoplasm to characterize the putative cytoplasmic non-genomic function of ERalpha. We have found that the cytoplasmic ERalpha can bind estrogen and is down-regulated, similar to wild-type ERalpha. However, the cytoplasmic ERalpha cant activate gene transcription due to its inability to enter the nucleus, and also cant stimulate cell cycle progression or proliferation. Consistent with the cytoplasmic ERalpha not activating gene transcription or cell cycle progression, cytoplasmic ERalpha is not able to induce the estrogen-regulated genes cyclin D1 or IRS-1. We are now determining whether the cytoplasmic ERalpha is able to interact with cytoplasmic signaling intermediates and confer non-genomic signaling, and also whether localization of ERalpha specifically to the membrane can enhance the non-genomic actions of ERalpha.
- Medicine and Medical Research