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Use of protein profiles to characterise the concentration effects curve for mixtures of estrogenic compounds
Project Code: T10004;
1. Zhu Z, Edwards RJ, Boobis AR. (2009). Increased expression of histone proteins during estrogen-mediated cell proliferation. Environ. Health Perspect. 117(6):928-34. Epub 2009 Feb 7.
2. Zhu, Z., Edwards, R.J., Boobis, A.R. (2008) Proteomic analysis of human breast cell lines using SELDI-TOF MS shows that mixtures of estrogenic compounds exhibit simple similar action (concentration additivity).
Toxicology Lett. 181 (2): 93-103.
3. Zhu, Z., Boobis, A.R., Edwards, R.J. (2008) Identification of estrogen-responsive proteins in MCF-7 human breast cancer cells using label-free quantitative proteomics. Proteomics 8 (10): 1987-2005.
Section of Experimental Medicine and Toxicology, Imperial College London
Boobis, A ;
Imperial College London
The possibility that mixtures of dietary chemicals, such as estrogenic compounds, act synergistically is a cause for concern. Such chemicals act directly, via estrogen receptors, or indirectly to modulate expression of estrogen-responsive genes. If successful this work would reveal how the proteome of the cell responds to mixtures of estrogenic compounds and fully characterise the concentration-effect curve. This project utilised a novel approach to conduct a mechanistically-based investigation into the effects of low concentrations of combinations of estrogenic chemicals, determining the profile of expressed proteins in human breast tumour cell lines. Protein profiling of cell lines varying in estrogen receptor status would be undertaken using using surface-enhanced laser desorption/ionisation – time of flight (SELDI-TOF) mass spectrometry. Those proteins changing significantly would be identified by conventional proteomic techniques and assessed for biological relevance. This could form the basis of a new way of assessing responsiveness.
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