Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells.

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Sharan S, Nikhil K, Roy P

Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells.

Toxicol Appl Pharmacol. 2013 Jun 1;269(2):176-86. doi: 10.1016/j.taap.2013.03.009. Epub 2013 Mar 21.

PubMed ID
23523586 [ View in PubMed
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Abstract

Endocrine disrupting chemicals are the natural/synthetic compounds which mimic or inhibit the actions of endogenous hormones. Organotin compounds, such as tributyltin (TBT) are typical environmental contaminants and suspected endocrine-disrupting chemical. The present study evaluates the estrogenic potential of this compound in vitro in ER (+) breast adenocarcinoma, MCF-7 cell line. Our data showed that tributyltin chloride (TBTCl) had agonistic activities for estrogen receptor-alpha (ER-alpha). Its estrogenic potential was checked using cell proliferation assay, aromatase assay, transactivation assay, and protein expression analysis. Low dose treatment of TBTCl had a proliferative effect on MCF-7 cells and resulted in up-regulation of aromatase enzyme activity and enhanced estradiol production in MCF-7 cells. Immunofluorescence staining showed translocation of ER-alpha from cytoplasm to nucleus and increased expression of ER-alpha, 3beta-HSD and aromatase on treatment with increasing doses of TBTCl. Further, to decipher the probable signaling pathways involved in its action, the MCF-7 cells were transfected with different pathway dependent luciferase reporter plasmids (CRE, SRE, NF-kappaB and AP1). A significant increase in CRE and SRE and decrease in NF-kappaB regulated pathway were observed (p<0.05). Our results thus showed that the activation of SRE by TBTCl may be due to ligand dependent ER-alpha activation of the MAPK pathway and increased phosphorylation of ERK. In summary, the present data suggests that low dose of tributyltin genomically and non-genomically augmented estrogen dependent signaling by targeting various pathways.