title: Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells.
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-α (ER-α). 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-α from cytoplasm to nucleus and increased expression of ER-α, 3β-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-κB and AP1). A significant increase in CRE and SRE and decrease in NF-κB 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-α 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.
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Sharan
authors.forename: Kumar
authors.initials: K
authors.lastname: Nikhil
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D011960:Receptors, Estrogen; D014220:Trialkyltin Compounds; C011559:tributyltin; D015096:3-Hydroxysteroid Dehydrogenases