title: ERα36, a new variant of the ERα is expressed in triple negative breast carcinomas and has a specific transcriptomic signature in breast cancer cell lines.
abstract: Triple negative breast cancer is deprived of estrogen receptor alpha (ERα), progesterone receptor (PR) and HER-2 protein. It constitutes the most heterogeneous and aggressive group of breast carcinomas, for which identification of novel characteristics and characterization of putative targets becomes very demanding. In the present work we have assayed the expression of ERα36, a recently identified ERα variant of 36kDa, in a series of triple negative breast cancers, in relation to the clinical behavior and other clinico-pathological features of the tumors. While widely expressed within the cytoplasm in almost all tumors, we found that exclusively the membrane/submembrane expression of the receptor exhibits a correlation with patient's survival. Moreover, membrane ERα36 correlates in an inverse manner with the expression of miRNA210, a pro-angiogenic miR, with high prognostic relevance in triple negative carcinomas. A thorough transcriptomic, pharmacological-based approach in breast cancer cell lines, revealed an early (direct) transcriptional signature of the receptor activation, related to immune system processes and T-cell differentiation, RNA biosynthesis, regulation of metabolism, VEGF signaling and regulation of the cell cycle, with a down-regulation of CREB, NFκB and STATs transcription factors. Finally, ERα36 expression is not limited within breast cancer epithelial linen, but is equally identified in tumor vasculature, peritumoral fat tissue, lymphocytic infiltrate and stromal fibroblasts. In light of the above, ERα36 could represent a major counterpart in triple negative breast cancer.
authors.affiliation: Laboratories of Pathology, University of Crete, School of Medicine, Heraklion, Greece. pelekanou@med.uoc.gr
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pelekanou
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Tsentelierou
authors.forename: Jelena
authors.initials: J
authors.lastname: Radojicic
authors.forename: Guy
authors.initials: G
authors.lastname: Leclercq
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
authors.forename: Efstathios N
authors.initials: EN
authors.lastname: Stathopoulos
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D053858:Metabolic Networks and Pathways; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D059467:Transcriptome
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D020033:Protein Isoforms