Novel Mechanisms by Which Estrogen Induces Antiapoptosis in Breast Cancer
Abstract
We investigated the mechanisms of membrane estrogen receptor signaling to breast cancer. We discovered that serine 522 of mouse ER alpha is required for membrane localization. Importantly, when expressed in MCF-7 cells, this S522A mutant ER alpha endogenous ER alpha, sequestering it from the membrane and inhibiting ERK activation by E2. This mutant has no effect on endogenous nuclear ER. We found that cyclin D1 synthesis, Cdk4 activity and G1/S progression is stimulated via ERK and inhibited by S522A mutant ER alpha expression in MCF-7 (Mol Cell Biol 23(3):1633-46, 2003). We also found that estradiol signaling to ERK involves transactivation of the EGF receptor, through Gq alpha and Gi alpha signaling to Src, Mmp activation and HB-EGF liberation. Only the E domain of ER alpha is required for these events initiated at the plasma membrane (J Biol Chem 278:2701-12, 2003) More recently, we showed that BRCA1 inhibits membrane ER and growth factor signaling through ERK to cell proliferation and this is lost when BRCA1 is mutated (MCB, July 2004, In press).
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA427966
Entities
People
- Ellis R. Levin
Organizations
- University of California, Irvine