Comparative analysis of nuclear estrogen receptor alpha and beta interactomes in breast cancer cells

Giovanni Nassa; Roberta Tarallo; Pietro H. Guzzi; Lorenzo Ferraro; Francesca Cirillo; Maria Ravo; Ernesto Nola; Marc Baumann; Tuula A. Nyman; Mario Cannataro; Concetta Ambrosino; Alessandro Weisz

doi:10.1039/C0MB00145G

Comparative analysis of nuclear estrogen receptor alpha and beta interactomes in breast cancer cells†

Giovanni Nassa,‡^a Roberta Tarallo,‡^a Pietro H. Guzzi,^b Lorenzo Ferraro,^a Francesca Cirillo,^a Maria Ravo,^a Ernesto Nola,^a Marc Baumann,^c Tuula A. Nyman,^d Mario Cannataro,^be Concetta Ambrosino^f and Alessandro Weisz*^ag

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* Corresponding authors

^a Department of General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Napoli, Italy
E-mail: alessandro.weisz@unina2.it
Fax: +39 081 441655
Tel: +39 081 441655

^b Department of Experimental and Clinical Medicine, Bioinformatics Laboratory, University ‘Magna Graecia’, Catanzaro, Italy

^c Protein Chemistry Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

^d Protein Chemistry Research Group, Institute of Biotechnology, University of Helsinki, Helsinki, Finland

^e ICAR, CNR, Rende, Italy

^f Department of Biological and Environmental Sciences, University of Sannio, Benevento, Italy

^g Molecular Medicine Laboratory, Faculty of Medicine and Surgery, University of Salerno, Baronissi, Italy

Abstract

Estrogen Receptor alpha and beta (ER-α and -β) are members of the nuclear receptor family of transcriptional regulators with distinct roles in mediating estrogen dependent breast cancer cell growth and differentiation. Following activation by the hormone, these proteins undergo conformation changes and accumulate in the nucleus, where they bind to chromatin at regulatory sites as homo- and/or heterodimers and assemble in large multiprotein complexes. Although the two ERs share a conserved structure, they exert specific and distinct functional roles in normal and transformed mammary epithelial cells and other cell types. To investigate the molecular bases of such differences, we performed a comparative computational analysis of the nuclear interactomes of the two ER subtypes, exploiting two datasets of receptor interacting proteins identified in breast cancer cell nuclei by Tandem Affinity Purification for their ability to associate in vivo with ligand-activated ER-α and/or ER-β. These datasets comprise 498 proteins, of which only 70 are common to both ERs, suggesting that differences in the nature of the two ER interactomes are likely to sustain the distinct roles of the two receptor subtypes. Functional characterization of the two interactomes and their topological analysis, considering node degree and closeness of the networks, confirmed this possibility. Indeed, clustering and network dissection highlighted the presence of distinct and ER subtype-specific subnetworks endowed with defined functions. Altogether, these data provide new insights on the protein–protein interaction networks controlled by ER-α and -β that mediate their ability to transduce estrogen signaling in breast cancer cells.

This article is part of the themed collection: Italian Proteomics Association

Molecular BioSystems

Comparative analysis of nuclear estrogen receptor alpha and beta interactomes in breast cancer cells†

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Comparative analysis of nuclear estrogen receptor alpha and beta interactomes in breast cancer cells

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