ERβ Effects on Alternative Splicing in Breast Cancer
1. Translational Medicine @ UniSa - ISSN 2239-9747 2014, Special Issue (1): 56
Giornate della Facoltà di Farmacia e Medicina a Salerno
Campus di Fisciano dell'Università di Salerno presso il Dipartimento di Farmacia
22 e 23 maggio 2014
56
Università degli Studi di Salerno
Analysis by RNA-Seq of Ligand-Actived Estrogen Receptor Beta (ERβ) Effects
on Alternative Splicing Patterns in Breast Cancer Cells
Santamaria G1, Rinaldi A1, Dago DN1,2, Giurato G1, Ravo M1, Ricciardi L1, Cordella A1,3, Weisz A1
1Department of Medicine and Surgery, Laboratory of Molecular Medicine and Genomics, University of
Salerno, Baronissi (SA), Italy;
2 UFR Sciences Biologiques, Université Peleforo Gon Coulibaly, Korhogo, Costa d'Avorio;
3Fondazione IRCCS SDN, Napoli (NA), Italy.
RNA-Seq is a powerful technology for gene expression profiling. In addition, the sequence read
length and coverage allowed by current sequencing technologies allows also an accurate estimation
of RNA isoforms generated by alternative splicing (AS).
AS contributes to the complexity of higher eukaryotes and its disruption is a major source of human
disease. AS is the process in which a pre-mRNA transcripts can be spliced in different ways to
obtain various new mRNAs. Spliceosome activity has been shown to depend upon a large number
of components, including hnRNPs (heterogeneous nuclear ribonucleoproteins), SR proteins
(serine/arginine-rich proteins) and U1, U2, U3 and U4 spliceosomal small nuclear
ribonucleoproteins. Recent studies have demonstrated that significant changes in AS events are
related to breast cancer (BC), suggesting that an understanding of these events could increase
prognosis accuracy and open new frontiers for research in molecular oncology.
Previous genomics and proteomics studies revealed that the different biological activity of estrogen
receptor (ER) β respect to α relies also on components of the splicing machinery, confirming the
relationship between ERβ and mRNA splicing.
To examine these events in a controlled environment, we investigated splicing events specifically
affected by ERβ in hormone-responsive breast cancer cells to search for novel insights on the
effects of this receptor on the biological and clinical phenotype of tumors. Results show that a
significant number of splicing events are either induced or prevented by ERβ in these cells,
indicating an impact of this ER subtype on post-transcriptional gene regulation via AS in hormone-
responsive BC.
RESEARCH SUPPORTED BY: AIRC (Grant IG-13176), MIUR (PRIN 2010LC747T_002), EU
COST (Action BM1006 ‘SeqAhead’), CNR InterOmics Flagship Project and a ‘Vladimir
Ashkenazy’ AIRC fellowship (to M. Ravo).
