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Bisphenol A stimulates human prostate cancer cell migration via remodelling of calcium signalling

Sandra Derouiche12, Marine Warnier12, Pascal Mariot12, Pierre Gosset3, Brigitte Mauroy4, Jean-Louis Bonnal4, Christian Slomianny12, Philippe Delcourt12, Natalia Prevarskaya12 and Morad Roudbaraki12*

Author Affiliations

1 Inserm, U-1003, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d’Ascq, France

2 Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d’Ascq, France

3 Laboratoire d’Anatomie et de Cytologie Pathologique du groupement hospitalier de l’Institut Catholique de Lille, Faculté Libre de Médecine, Lille, France

4 Service d’Urologie de l’hôpital St-Philibert, Lomme, France

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SpringerPlus 2013, 2:54  doi:10.1186/2193-1801-2-54

Published: 15 February 2013

Abstract

Bisphenol A (BPA), the principal constituent of reusable water bottles, metal cans, and plastic food containers, has been shown to be involved in human prostate cancer (PCa) cell proliferation. The aim of the present study was to explore the effect of BPA on PCa cell migration and the pathways involved in these processes. Using the transwell technique, we clearly show for the first time that the pre-treatment of the cells with BPA (1–10 nM) induces human PCa cell migration. Using a calcium imaging technique, we show that BPA pre-treatment induces an amplification of Store-Operated Calcium Entry (SOCE) in LNCaP cells. RT-PCR and Western blot experiments allowed the identification of the ion channel proteins which are up-regulated by BPA pre-treatments. These include the Orai1 protein, which is known as an important SOCE actor in various cell systems, including human PCa cells. Using a siRNA strategy, we observed that BPA-induced amplification of SOCE was Orai1-dependent. Interestingly, the BPA-induced PCa cell migration was suppressed when the calcium entry was impaired by the use of SOCE inhibitors (SKF96365, BTP2), or when the extracellular calcium was chelated. Taken together, the results presented here show that BPA induces PCa cells migration via a modulation of the ion channel protein expression involved in calcium entry and in cancer cell migration. The present data provide novel insights into the molecular mechanisms involved in the effects of an environmental factor on cancer cells and suggest both the necessity of preventive measures and the possibility of targeting ion channels in the treatment of PCa cell metastasis.

Keywords:
Environmental factors; Bisphenol A; Cell migration; Calcium signalling; Ion channels; Orai1; Prostate cancer