Arsenic induces functional re-expression of estrogen receptor α by demethylation of DNA in estrogen receptor-negative human breast cancer.

PloS One
Juan DuZhong Li

Abstract

Estrogen receptor α (ERα) is a marker predictive for response of breast cancers to endocrine therapy. About 30% of breast cancers, however, are hormone- independent because of lack of ERα expression. New strategies are needed for re-expression of ERα and sensitization of ER-negative breast cancer cells to selective ER modulators. The present report shows that arsenic trioxide induces reactivated ERα, providing a target for therapy with ER antagonists. Exposure of ER-negative breast cancer cells to arsenic trioxide leads to re-expression of ERα mRNA and functional ERα protein in in vitro and in vivo. Luciferase reporter gene assays and 3-(4,5-dimethylthiazol-2-yl)- 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays show that, upon exposure to arsenic trioxide, formerly unresponsive, ER-negative MDA-MB-231 breast cancer cells become responsive to ER antagonists, 4-hydroxytamoxifen and ICI 182,780. Furthermore, methylation- specific PCR and bisulfite-sequencing PCR assays show that arsenic trioxide induces partial demethylation of the ERα promoter. A methyl donor, S-adenosylmethionine (SAM), reduces the degree of arsenic trioxide-induced re-expression of ERα and demethylation. Moreover, Western blot and ChIP ...Continue Reading

References

Jul 1, 1992·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S R JohnstonI E Smith
Feb 1, 1984·The Journal of Pharmacy and Pharmacology·P A CrooksR J Pinney
Jan 15, 1981·International Journal of Cancer. Journal International Du Cancer·R J Hastings, L M Franks
Mar 15, 1995·Journal of the National Cancer Institute·N RoodiF F Parl
Sep 30, 1995·Annals of the New York Academy of Sciences·J FishmanN T Telang
May 20, 2000·Journal of Mammary Gland Biology and Neoplasia·R G LapidusN E Davidson
Jul 14, 2001·Nucleic Acids Research·C M Klinge
May 16, 2002·Seminars in Hematology·Kelly DavisonWilson H Miller
Jun 13, 2002·British Journal of Haematology·Maria I González-FraileJesús F San Miguel
Aug 3, 2002·Oncogene·Martin Widschwendter, Peter A Jones
Dec 31, 2002·Toxicology·Marie Vahter
Nov 13, 2003·Cancer Science·Mariko KitoYukihiro Akao
Jun 23, 2004·Critical Reviews in Oncology/hematology·Nadine PlatetMarcel Garcia
Jan 13, 2006·The Oncologist·Laura GiacintiAntonio Giordano
Sep 28, 2006·Breast Cancer Research and Treatment·James M RaeMichael D Johnson
Nov 3, 2007·The Journal of Clinical Investigation·Kornelia Polyak
May 5, 2009·Cancer Biology & Therapy·Madhavi BillamNancy E Davidson
Nov 11, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Seyed H GhaffariKamran Alimoghaddam
Apr 29, 2015·Turkish Journal of Haematology : Official Journal of Turkish Society of Haematology·Hakan SavlıMario Petrini
Oct 12, 2015·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Jianhua ZouZhe Chen

❮ Previous
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Citations

Feb 13, 2014·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Lalit P ChandravanshiVinay K Khanna
Apr 3, 2014·Archives of Toxicology·Elisa BustaffaLucia Migliore
Jun 27, 2014·Journal of Developmental Origins of Health and Disease·K BrobergM Vahter
Sep 3, 2014·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Lalit P ChandravanshiVinay K Khanna
Jan 13, 2015·EBioMedicine·Allan H SmithCatterina Ferreccio
Jun 3, 2015·Environmental and Molecular Mutagenesis·Rogelio Recio-VegaGladis Michel-Ramirez
Jul 19, 2013·Pharmaceutical Biology·Srabanti MondalPrabir Kumar Mukhopadhyay
Sep 16, 2017·Artificial Cells, Nanomedicine, and Biotechnology·Sania NazMuhammad Zia
Jun 13, 2013·Environmental Health Perspectives·Devin C KoestlerCarmen J Marsit
Sep 7, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Moonmoon DebSamir Kumar Patra
Nov 19, 2019·Current Cancer Drug Targets·Md WahiduzzamanYoshitaka Hosokawa
Feb 10, 2017·Oncotarget·Adam P SageVictor D Martinez
Aug 21, 2020·Environmental Science and Pollution Research International·Jingwen TanYuefeng He
Nov 26, 2016·Bioscience Reports·Vijaya Narasihma Reddy GajulapalliBramanandam Manavathi
May 5, 2016·Molecular Nutrition & Food Research·Donato F RomagnoloOrnella I Selmin
Oct 10, 2020·Environmental Geochemistry and Health·Mengjie WangYuefeng He
Sep 15, 2019·Environmental Research·Alina-Andreea ZimtaIoana Berindan-Neagoe
May 29, 2020·Seminars in Cancer Biology·Kah Keng Wong
Jul 27, 2021·Environmental Science and Pollution Research International·Nasreddine El OmariAbdelhakim Bouyahya
Mar 29, 2019·Chemical Research in Toxicology·Jun XiongYu-Qi Feng

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Methods Mentioned

BETA
ChIP
Immunoprecipitation
transfection
Assay
xenograft
PCR
electrophoresis
Protein Assay

Software Mentioned

Methyl Primer Express
MethPrimer

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