Moonlighting Proteins and Cardiopathy in the Spatial Response of MCF-7 Breast Cancer Cells to Tamoxifen

Abstract

Background: The purpose of this study is to apply quantitative high-throughput proteomics methods to investigate dynamic aspects of protein changes in nucleocytoplasmic distribution of proteins and of total protein abundance for MCF-7 cells exposed to tamoxifen (Tam) in order to reveal the agonistic and antagonistic roles of the drug.

Experimental design: The MS-based global quantitative proteomics with the analysis of fractions enriched in target subcellular locations is applied to measure the changes in total abundance and in the compartmental abundance/distribution between the nucleus and cytoplasm for several thousand proteins differentially expressed in MCF-7 cells in response to Tam stimulation.

Results: The response of MCF-7 cells to the Tam treatment shows significant changes in subcellular abundance rather than in their total abundance. The bioinformatics study reveals the relevance of moonlighting proteins and numerous pathways involved in Tam response of MCF-7 including some of which may explain the agonistic and antagonistic roles of the drug.

Conclusions: The results indicate possible protective role of Tam against cardiovascular diseases as well as its involvement in G-protein coupled receptors pathways that enhance breast tissue proliferation.

Keywords: MCF-7 cells; SILAC-based quantitative proteomics; mass spectrometry; subcellular protein location; tamoxifen.