The RNA binding protein CPEB2 regulates hormone sensing in mammary gland development and luminal breast cancer
Open Access
- 1 May 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (20), eaax3868
- https://doi.org/10.1126/sciadv.aax3868
Abstract
Organogenesis is directed by coordinated cell proliferation and differentiation programs. The hierarchical networks of transcription factors driving mammary gland development and function have been widely studied. However, the contribution of posttranscriptional gene expression reprogramming remains largely unexplored. The 3' untranslated regions of messenger RNAs (mRNAs) contain combinatorial ensembles of cis-regulatory elements that define transcript-specific regulation of protein synthesis through their cognate RNA binding proteins. We analyze the contribution of the RNA binding cytoplasmic polyadenylation element-binding (CPEB) protein family, which collectively regulate mRNA translation for about 30% of the genome. We find that CPEB2 is required for the integration of hormonal signaling by controlling the protein expression from a subset of ER/PR- regulated transcripts. Furthermore, CPEB2 is critical for the development of ER-positive breast tumors. This work uncovers a previously unknown gene expression regulation level in breast morphogenesis and tumorigenesis, coordinating sequential transcriptional and posttranscriptional layers of gene expression regulation.Funding Information
- Fundación BBVA
- Spanish Ministry of Economy and Competitiveness (BFU2014-54122-P/ BFU2017-83561-P)
- Worldwide Cancer Research Foundation
- AECC
- La Caixa Foundation
- Fundación Botín, the Banco Santander
- la Caixa” predoctoral fellowship
This publication has 79 references indexed in Scilit:
- TMARKER: A free software toolkit for histopathological cell counting and staining estimationJournal of Pathology Informatics, 2013
- Application of whole slide image markup and annotation for pathologist knowledge captureJournal of Pathology Informatics, 2013
- The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroupsNature, 2012
- Fast gapped-read alignment with Bowtie 2Nature Methods, 2012
- A framework for oligonucleotide microarray preprocessingBioinformatics, 2010
- Targeting RANKL to a specific subset of murine mammary epithelial cells induces ordered branching morphogenesis and alveologenesis in the absence of progesterone receptor expressionThe FASEB Journal, 2010
- Two distinct mechanisms underlie progesterone-induced proliferation in the mammary glandProceedings of the National Academy of Sciences of the United States of America, 2010
- The RANKL signaling axis is sufficient to elicit ductal side-branching and alveologenesis in the mammary gland of the virgin mouseDevelopmental Biology, 2009
- GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary GlandCell, 2006
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005