AHR and GPER mediate the stimulatory effects induced by 3-methylcholanthrene in breast cancer cells and cancer-associated fibroblasts (CAFs)

Journal of Experimental & Clinical Cancer Research : CR
Francesca CirilloMarcello Maggiolini

Abstract

The chemical carcinogen 3-methylcholanthrene (3MC) binds to the aryl hydrocarbon receptor (AHR) that regulates the expression of cytochrome P450 (CYP) enzymes as CYP1B1, which is involved in the oncogenic activation of environmental pollutants as well as in the estrogen biosynthesis and metabolism. 3MC was shown to induce estrogenic responses binding to the estrogen receptor (ER) α and stimulating a functional interaction between AHR and ERα. Recently, the G protein estrogen receptor (GPER) has been reported to mediate certain biological responses induced by endogenous estrogens and environmental compounds eliciting an estrogen-like activity. Molecular dynamics and docking simulations were performed to evaluate the potential of 3MC to interact with GPER. SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) derived from breast tumor patients were used as model system. Real-time PCR and western blotting analysis were performed in order to evaluate the activation of transduction mediators as well as the mRNA and protein levels of CYP1B1 and cyclin D1. Co-immunoprecipitation studies were performed in order to explore the potential of 3MC to trigger the association of GPER with AHR and EGFR. Luciferase assays were carr...Continue Reading

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Citations

Apr 7, 2020·Expert Opinion on Therapeutic Targets·Rosamaria LappanoErnestina Marianna De Francesco
Sep 26, 2020·Frontiers in Endocrinology·Séverine Périan, Jean-Marc Vanacker
Jan 15, 2020·Journal of Experimental & Clinical Cancer Research : CR·Chi ShuBo Zhu
Aug 12, 2020·Journal of Experimental & Clinical Cancer Research : CR·Rosamaria LappanoMarcello Maggiolini
Aug 28, 2020·Frontiers in Endocrinology·Fedora GrandeBruno Rizzuti
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Giulia D'ArrigoFrancesca Spyrakis
Jul 24, 2021·European Journal of Pharmacology·Shaojie YangGuoqi Zhu

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Methods Mentioned

BETA
PCR
protein assay
immunoprecipitation
Transfection
co-immunoprecipitation
nuclear translocation

Software Mentioned

GPCR
Primer Express
AutoDock Vina
GROMACS
GPER
Quant Studio7 Flex Real PCR
AMBER
TASSER
GAFF
AutoDock Tools

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