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

TitleERα36, a new variant of the ERα is expressed in triple negative breast carcinomas and has a specific transcriptomic signature in breast cancer cell lines
Publication TypeJournal Article
Year of Publication2012
AuthorsPelekanou, V, Notas G, Kampa M, Tsentelierou E, Radojicic J, Leclercq G, Castanas E, Stathopoulos EN
JournalSteroids
Volume77
Issue10
Pages928 - 934
KeywordsBreast cancer (triple negative), Breast cancer survival, Estrogen receptors, Gene signature, microRNA
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 36 kDa, 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. © 2011 Elsevier Inc. All rights reserved.

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