Evidence of cross-talk between AhR and ER signaling pathways in fish and human reporter cell lines used for estrogenicity screening

Abstract : In vitro cellular assays based on the stable expression of a reporter gene driven by estrogen receptor (ER) are recognized as valuable effect-based tools (EBT) to assess estrogenic activity of environmental mixtures. However, it is now established that ER-mediated cellular response can be influenced by different factors relative to the cell context studied, such as metabolism and cross-talk with other cellular signaling pathways. AhR ligands (i.e. dioxin-like compounds) are widespread environmental contaminants and generally occur concomitantly with estrogenic compounds. Interactions between aryl hydrocarbon receptor (AhR) and ER signaling pathways have been reported in numerous studies, both in fish and human. Characterizing such interferences in EBT used for estrogenicity screening appears crucial when interpreting ER cellular response to complex environmental mixtures. Our work aims at characterizing three recently established zebrafish reporter cell lines stably transfected with zfERα (ZELHα), zfERß1 (ZELHß1) or zfERß2 (ZELHß2) subtypes (1) by comparing response profiles between human (MELN derived from MCF-7) and zebrafish (ZFL zebrafish liver cells) cellular contexts and (2) by assessing possible influence of zfER subtypes on the response, especially in case of zfERß2, a fish-specific ER subtype.