Abstract
Abstract Tetraspanin is a four transmembrane protein family whose members are regarded as molecular linkers. They also serve as scaffold proteins for many signaling processes. CD63 is a member of the tetraspanin family that serves as a lysosomal protein. Estrogen receptor alpha (ERα) plays critical roles in breast carcinogenesis. Extranuclear ERα could initiate rapid estrogen responses by forming protein complexes with many signaling molecules. Here, we report a novel protein complex formed between tetraspanin CD63 and extranuclear ERα. Immunoprecepitation (IP) experiments in MCF-7 and BT474 cells showed that CD63 interacts with ERα at endogenous levels. IP experiments using extracts from different cellular compartments (nucleus, cytoplasm and plasma membrane) showed that the interaction between CD63 and ERα is mainly located on the plasma membrane. Moreover, using co-immunofluorescence (IF) staining, we found CD63 co-localized with ERα on plasma membrane and/or in the cytoplasm. To further explore the effects of CD63 on ERα signaling pathways, we stably knocked down CD63 by shRNA in MCF-7 and BT474 cells. Interestingly, the expression of ERα was increased with lower expression of CD63. We further examined ERα from extracts of nucleus, cytoplasm, and membrane by western blots, and found that ERα in cytoplasm and/or membrane was increased by knocking down CD63 whereas the ERα level in the nucleus was not changed. IF staining showed similar results. Furthermore, P-MAPK level was up-regulated in both MCF-7 and BT474 cell lines with suppressed expression of CD63. These data suggest that the tetraspanin CD63 may facilitate the transport of ERα between plasma membrane and/or cytoplasm and nucleus, an important new function. CD63 may play a key role on organizing and regulating non-genomic ERα signaling pathways in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1210. doi:1538-7445.AM2012-1210
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