Abstract
Objective:
To determine the relationship between papillary thyroid carcinoma and environmental exposure to bisphenol A (BPA) or 17-β estrogen (E2) by assessing the effects of these compounds on estrogen receptor expression and AKT/mTOR signaling.
Methods:
The effects of low levels of BPA (1mM-10nM) and 17β-estradiol (E2, 0.1mM-1nM) on ER expression and cellular proliferation were determined in human thyroid papillary cancer BHP10-3 cells. Protein and mRNA levels of estrogen nuclear receptors (ERα/ERβ) and membrane receptors (GPR30) were determined by immunofluorescence assay, Western blotting, and RT-PCR, respectively, and proliferation was assessed by CCK-8 assay.
Results:
The proliferative effects of BPA and E2 were both concentration- and time-dependent. Expression of ERα/ERβ and GPR30 were enhanced by BPA and E2. BPA and E2 could quickly phosphorylate AKT/mTOR. Moreover, ICI suppressed ERα expression and activated GPR30 as did G-1. G-15 reversed the effects of E2 on GPR30 and AKT/mTOR, but did not alter the effect of BPA.
Conclusions:
BPA influences thyroid cancer proliferation by regulating expression of ERs and GPR30, a mechanism that differs from E2. In addition, ICI and G-15 may have the potential to be used as anti-thyroid cancer agents.
Keywords:
AKT; Bisphenol A; Estrogen receptor; Thyroid cancer; mTOR.
Copyright © 2017 Elsevier Inc. All rights reserved.
MeSH terms
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Air Pollutants, Occupational / pharmacology*
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Benzhydryl Compounds / pharmacology*
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Benzodioxoles / pharmacology
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Estradiol / analogs & derivatives
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Estradiol / pharmacology*
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Estrogen Receptor alpha / agonists
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Estrogen Receptor alpha / genetics*
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Estrogen Receptor alpha / metabolism
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Estrogen Receptor beta / agonists
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Estrogen Receptor beta / genetics*
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Estrogen Receptor beta / metabolism
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Fulvestrant
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Gene Expression Regulation, Neoplastic*
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Humans
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Phenols / pharmacology*
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Quinolines / pharmacology
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Receptors, Estrogen / antagonists & inhibitors
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism
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Receptors, G-Protein-Coupled / antagonists & inhibitors
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Signal Transduction
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TOR Serine-Threonine Kinases / antagonists & inhibitors
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism
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Thyroid Epithelial Cells / drug effects*
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Thyroid Epithelial Cells / metabolism
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Thyroid Epithelial Cells / pathology
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Time Factors
Substances
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4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline
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Air Pollutants, Occupational
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Benzhydryl Compounds
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Benzodioxoles
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ESR1 protein, human
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Estrogen Receptor alpha
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Estrogen Receptor beta
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GPER1 protein, human
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Phenols
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Quinolines
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Receptors, Estrogen
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Receptors, G-Protein-Coupled
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Fulvestrant
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Estradiol
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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bisphenol A