Membrane Estrogen Receptor Alpha Targeting and its Association with SHC in Regulating Breast Cancer Cell Proliferation
Annual rept. 6 May 2003-5 May 2004
NORTH CAROLINA UNIV AT CHARLOTTE
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Estrogen receptor a, ERa, the dominant isoform in mammary gland, is a dual functional protein capable of acting as a transcriptional factor regulating gene transcription in the nucleus genomic effect, or a signaling molecule on the membrane mediating estrogen rapid actions non-genomic effect to activate MAPK and Akt pathways. Currently, the functions of the nuclear ERa is very well studied, but the biological role of the membrane-associated ERa is still not clear due to the fact that all ERa-expressing cells have both nuclear and membrane ones co-expressed. One way to investigate the biological role of the membrane-associated ERa in breast cancer cells is to develop a cell line that only express the ERa on the cell membrane or in the cytosol Designer cells. The goal of this proposal is to develop designer COS-l cells, which lack endogenous ERa, with constructs that express forms of the ERa that are specifically cytosolic or membrane-associated, and use these tools in experiments designed to elucidate the functional roles of the membrane-associated, or cytosol ERa, especially its role in interacting and activating Shc adapter protein, leading to MAP kinase activation.
- Anatomy and Physiology
- Medicine and Medical Research