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Identifier 000426883
Title The intracellular trafficking of G protein-coupled estrogen receptor 1, GPER1
Alternative Title Η ενδοκυττάρια διακίνηση του υποδοχέα οιστρογόνων που συνδέεται με G πρωτεΐνες, GPER1
Author Βαμβουκάκη, Ροδάνθη
Thesis advisor Νότας, Γεώργιος
Abstract Estrogen receptors (ERs) are essential regulators of breast carcinogenesis. ERs include the two classic nuclear receptors, ERα and ERβ, and the membrane G-protein coupled estrogen receptor 1 (GPER1). GPER1 has been reported to initiate rapid non-genomic estrogen-related effects and activate several intracellular pathways. GPER1 is present on the cellular membrane but was also found in intracellular organelles, including the endoplasmic reticulum and the Golgi apparatus. Recently, translocation of GPER1 into the nucleus has also been suggested, but conclusive evidence is lacking, while its physiological relevance is unknown. Inflammation and NFκB activity are important for breast cancer growth. We have previously reported in monocytes that estrogen inhibits TLR4-dependent inflammation via interaction of the 36kD variant of ERα (ERα36) and GPER1 with NF- κB, thus leading to inhibition of its transcriptional activity. The aim of this study was to investigate the subcellular localization of GPER1 in breast cancer cell lines and its potential translocation to the nucleus by estrogen or TLR4 activation as well as its physical interaction with NFκΒ. Our results show that GPER1 translocates to the nucleus, after TLR4 activation, but not estradiol, treatment, in a time- and dose-dependent manner. Immunofluorescence with antibodies targeting the extracellular amino-terminal of GPER1 or its intracellular carboxy-terminal provides different patterns in GPER1 localization. Additionally, we confirm GPER1/NFκB co-localization inside the nucleus of breast cancer cells after TLR4 activation. Our data suggest that GPER1 translocates to the nucleus, where it may function as a potential regulator of NFκB pro-inflammatory transcriptional actions.
Language English
Subject Breast cancer
Καρκίνος Μαστού
Issue date 2019-12-11
Collection   Faculty/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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