A meta-analysis to evaluate the cellular processes regulated by the interactome of endogenous and over-expressed estrogen receptor alpha

Joana Simões1, Francisco M. Amado1,2, Rui Vitorino1,3,* and Luisa A. Helguero1,3,*

1 Mass Spectrometry Centre, QOPNA Research Unit, Department of Chemistry, Universidade de Aveiro, Campus Universitário de Santiago, Aveiro, Portugal

2 School of Healh Sciences, Universidade de Aveiro, Portugal

3 Institute for Research in Biomedicine - iBiMED, Health Sciences Program, Universidade de Aveiro, Portugal

* These authors are Senior authors


Luisa A. Helguero, email:

Keywords: estrogen receptor alpha, interactome, meta-analysis, breast cancer, mass spectrometry

Received: December 21, 2014 Accepted: March 04, 2015 Published: March 07, 2015


The nature of the proteins complexes that regulate ERα subcellular localization and activity is still an open question in breast cancer biology. Identification of such complexes will help understand development of endocrine resistance in ER+ breast cancer. Mass spectrometry (MS) has allowed comprehensive analysis of the ERα interactome. We have compared six published works analyzing the ERα interactome of MCF-7 and HeLa cells in order to identify a shared or different pathway-related fingerprint.

Overall, 806 ERα interacting proteins were identified. The cellular processes were differentially represented according to the ERα purification methodology, indicating that the methodologies used are complementary. While in MCF-7 cells, the interactome of endogenous and over-expressed ERα essentially represents the same biological processes and cellular components, the proteins identified were not over-lapping; thus, suggesting that the biological response may differ as the regulatory/participating proteins in these complexes are different. Interestingly, biological processes uniquely associated to ERα over-expressed in HeLa cell line included L-serine biosynthetic process, cellular amino acid biosynthetic process and cell redox homeostasis.

In summary, all the approaches analyzed in this meta-analysis are valid and complementary; in particular, for those cases where the processes occur at low frequency with normal ERα levels, and can be identified when the receptor is over-expressed. However special effort should be put into validating these findings in cells expressing physiological ERα levels.

PII: 138