The role of ERα36 in cell type-specific functions of estrogen and cancer development. (January 2021)

• Record Type: Journal Article
• Authors: Mahboobifard, Fatemeh; Dargahi, Leila; Jorjani, Masoumeh; Ramezani Tehrani, Fahimeh; Pourgholami, Mohammad H.
• Is Part Of: Pharmacological research. Volume 163(2021)
• Publication Date: 2021-01
• Subjects: ERs estrogen receptors -- ERα estrogen receptor alpha -- ERβ estrogen receptor beta -- SERMs selective estrogen receptor modulators -- NTD NH2-terminal domain -- DBD DNA-binding domain -- LBD ligand-binding domain -- OBs osteoblasts -- OCs osteoclasts -- MAPK/ERK mitogen-activated protein kinase/extracellular signal-regulated kinases -- PI3K/Akt phosphatidylinositol 3-kinase/ protein kinase B -- TNBC triple-negative breast cancer cells -- JNKs C-Jun N-Terminal Kinases -- EGFR epidermal growth factor receptor -- STAT5 signal transducer and activator of transcription 5 -- ROS retrospective observational study -- GPER G-protein estrogen receptor -- NFκB nuclear Factor of the κ-chain in B-cells -- MnSOD manganese-superoxide dismutase -- ht-UtLM human uterine leiomyoma -- IHC Immunohistochemistry -- PTC papillary thyroid carcinoma -- LPAs lactotroph pituitary adenomas -- PAC pure apocrine carcinomas -- ACC adenoid cystic carcinoma -- AIs aromatase inhibitors -- ALDH1A1 aldehyde dehydrogenase 1A1 -- LSCC Laryngeal Squamous cell cancer -- NSCLC Non-small cell lung cancer -- RCC Renal cell carcinoma -- HCC hepatocellular carcinoma -- SCC squamous cell carcinoma -- CSC cancer stem cell -- OGD oxygen and glucose deprivation -- MCAO middle cerebral artery occlusion -- H2O2 Hydrogen peroxide -- hPMs human primary monocytes -- RCH retrospective cohort study -- PCS prospective cohort study -- DFS disease-free survival -- DSS disease-specific survival -- MFS metastasis-free survival -- DMFS distant metastasis-free survival -- OS overall survival -- PgR progesterone receptor -- HER-2 human epidermal growth factor receptor 2 -- LNM lymph node metastasis -- GRP78 78kDa glucose-regulated protein -- wtERα wild type ERα -- ETE extrathyroidal extension -- TNM tumor nodes metastases -- TCGA the cancer genome atlas cohort -- Cy-3-glu Cyanidin-3-o-glucoside -- HP Huaier polysaccharide; Estradiol (PubChem CID: 5757) -- Tamoxifen (PubChem CID: 2733526) -- Fulvestrant (PubChem CID: 104741) -- Letrozole (PubChem CID: 3902) -- Paclitaxel (PubChem CID: 36314) -- Icaritin (CID: 5318980) -- Decitabine (CID: 451668) -- Cyanidin-3-o-glucoside (PubChem CID: 441667) -- Epigallocatechin-gallate (PubChem CID: 65064) -- Broussoflavonol B (PubChem CID: 480828); Estrogen receptor -- ERα36 -- ERα66 -- ERK kinetic -- Cancer -- Tamoxifen resistance; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105307
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Highlights: ERα36 mediates cell type-specific functions of estrogen through nongenomic signaling. ERα36 signaling is involved in cell survival and cell death, based on ERK kinetic. ERα36 signaling mediates neuroprotection and preserves bone density. Alterations in ERα36 expression levels in organs may promote cancer development. Profiling of ERα36 may be of diagnostic, prognostic and therapeutic value. Abstract: Exploring the regulatory effects of estrogen on different body organs via its receptors is largely of interest. Recently, the expression, signaling and the clinical significance of ERα36, the newly identified isoform of ERα, mediating non-genomic signaling of estrogen, have been studied in a wide range of organs and tumors. ERα36 is expressed highly in the CNS and actively involved in neuroprotection. It is also suggested to be an important estrogen receptor involved in preserving bone in postmenopausal women. On the oncological side, although ERα36 has usually been considered to be an oncogenic molecule, results from some studies paradoxically imply its protective role in certain tumors. Collectively, it seems that ERα36 is highly involved in cell type-specific functions of estrogen through its MAPK/ERK signaling, which is dependent on ERα36 expression levels, ligand concentrations and disease stage. The response is also dependent on the levels of ERα66 and ERβ. These factors influence the ERK kinetic and determine the ultimate mitogenic or antimitogenic signaling of estrogen, leading to cell survival or cell death. In this review, we summarize the recent organ-specific, cellular and molecular events and the mechanisms involved in estrogen effects mediated through the ERα36/ ERα66 with a particular focus on carcinomas where more clinical information has recently emerged.