title: Bisphenol AF-induced endogenous transcription is mediated by ERα and ERK1/2 activation in human breast cancer cells.
abstract: Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERα and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERα-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERα-positive T47D and MCF7 cells as well as overexpression of ERα in ERα-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcription of estrogen responsive genes is mediated through both genomic and nongenomic pathways involving the ERα and ERK1/2 activation in human breast cancer cells.
authors.affiliation: Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Emergency, Beijing Mentougou District Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Gao
authors.affiliation: Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing, China; School of Public Health and Family Medicine, Capital Medical University, Beijing, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Yu
authors.affiliation: Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing, China; School of Public Health and Family Medicine, Capital Medical University, Beijing, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Han
authors.affiliation: Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing, China; School of Public Health and Family Medicine, Capital Medical University, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shao
mesh_terms: D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D014158:Transcription, Genetic; D005466:Fluorocarbons; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D047628:Estrogen Receptor alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010636:Phenols; D048493:Proto-Oncogene Proteins B-raf; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C109584:GPER1 protein, human; C583074:bisphenol AF; D005466:Fluorocarbons; D000098826:Bisphenol A Compounds
references.citation: J Biol Chem. 2004 Jun 25;279(26):27008-16
references.pmid: 15090535
references.citation: Environ Health Perspect. 2010 Sep;118(9):1267-72
references.pmid: 20427257
references.citation: Curr Genomics. 2006;7(8):497-508
references.pmid: 18369406
references.citation: Cancer Res. 2007 Feb 15;67(4):1859-66
references.pmid: 17308128
references.citation: Toxicol Sci. 2010 Aug;116(2):477-87
references.pmid: 20498000
references.citation: J Clin Invest. 2012 Aug;122(8):2857-70
references.pmid: 22820289
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13057-62
references.pmid: 20616010
references.citation: Trends Endocrinol Metab. 2009 Dec;20(10):477-82
references.pmid: 19783454
references.citation: Mol Endocrinol. 1999 Oct;13(10):1672-85
references.pmid: 10517669
references.citation: N Engl J Med. 2006 Jan 19;354(3):270-82
references.pmid: 16421368
references.citation: Mol Endocrinol. 1996 Nov;10(11):1371-8
references.pmid: 8923463
references.citation: Toxicol Lett. 2012 Jun 1;211(2):201-9
references.pmid: 22504055
references.citation: Mol Cell Endocrinol. 2005 Jun 15;237(1-2):11-23
references.pmid: 15925090
references.citation: Environ Health Perspect. 2006 Jan;114(1):106-12
references.pmid: 16393666
references.citation: Mol Endocrinol. 2000 Oct;14(10):1649-60
references.pmid: 11043579
references.citation: Environ Health Perspect. 2012 Jul;120(7):1029-35
references.pmid: 22494775
references.citation: Environ Health Perspect. 2012 Aug;120(8):1177-82
references.pmid: 22552965
references.citation: Environ Health Perspect. 2013 Apr;121(4):459-66
references.pmid: 23384675
references.citation: Am J Pharmacogenomics. 2004;4(1):19-28
references.pmid: 14987119
references.citation: Toxicol Sci. 1999 Mar;48(1):55-66
references.pmid: 10330684
references.citation: J Biol Chem. 2000 Jun 16;275(24):18447-53
references.pmid: 10749889
references.citation: Toxicol Sci. 2005 Apr;84(2):249-59
references.pmid: 15635150
references.citation: J Steroid Biochem Mol Biol. 2002 Feb;80(2):231-8
references.pmid: 11897506
references.citation: Toxicol In Vitro. 2002 Oct;16(5):549-56
references.pmid: 12206822
references.citation: Science. 1997 Sep 5;277(5331):1508-10
references.pmid: 9278514
references.citation: PLoS One. 2013 Dec 13;8(12):e83170
references.pmid: 24349450
references.citation: Annu Rev Physiol. 2008;70:165-90
references.pmid: 18271749
references.citation: EMBO J. 2001 Nov 1;20(21):6050-9
references.pmid: 11689445
references.citation: J Steroid Biochem Mol Biol. 2006 Feb;98(2-3):97-110
references.pmid: 16414261
references.citation: PLoS One. 2008 Apr 30;3(4):e2069
references.pmid: 18446233
references.citation: Mol Cell Endocrinol. 2009 Sep 24;308(1-2):32-8
references.pmid: 19464786
references.citation: Environ Health Perspect. 2012 Mar;120(3):399-405
references.pmid: 22214767
references.citation: Blood. 1996 Dec 15;88(12):4676-83
references.pmid: 8977261
references.citation: Anal Chim Acta. 2011 Jun 24;696(1-2):6-26
references.pmid: 21621029
references.citation: Environ Sci Technol. 2012 Dec 18;46(24):13136-43
references.pmid: 23151244