Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells

Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected i...
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Gespeichert in:

Autor*in:	Lillo, M. Angeles [verfasserIn] Nichols, Cydney Seagroves, Tiffany N. Miranda-Carboni, Gustavo A. Krum, Susan A.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Cancer Stem Cell SOX2 Expression Breast Cancer Stem Cell Mammary Stem Cell Breast Stem Cell

Anmerkung:	© Springer Science+Business Media New York 2017

Übergeordnetes Werk:	Enthalten in: Hormones and cancer - New York, NY [u.a.] : Springer, 2010, 8(2017), 2 vom: 27. Feb., Seite 90-99
Übergeordnetes Werk:	volume:8 ; year:2017 ; number:2 ; day:27 ; month:02 ; pages:90-99

Links:	Volltext

DOI / URN:	10.1007/s12672-017-0286-5

Katalog-ID:	SPR027106586

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allfields	10.1007/s12672-017-0286-5 doi (DE-627)SPR027106586 (SPR)s12672-017-0286-5-e DE-627 ger DE-627 rakwb eng Lillo, M. Angeles verfasserin aut Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer Science+Business Media New York 2017 Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. Cancer Stem Cell (dpeaa)DE-He213 SOX2 Expression (dpeaa)DE-He213 Breast Cancer Stem Cell (dpeaa)DE-He213 Mammary Stem Cell (dpeaa)DE-He213 Breast Stem Cell (dpeaa)DE-He213 Nichols, Cydney aut Seagroves, Tiffany N. aut Miranda-Carboni, Gustavo A. aut Krum, Susan A. aut Enthalten in Hormones and cancer New York, NY [u.a.] : Springer, 2010 8(2017), 2 vom: 27. Feb., Seite 90-99 (DE-627)621547379 (DE-600)2543318-0 1868-8500 nnns volume:8 year:2017 number:2 day:27 month:02 pages:90-99 https://dx.doi.org/10.1007/s12672-017-0286-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 2 27 02 90-99
spelling	10.1007/s12672-017-0286-5 doi (DE-627)SPR027106586 (SPR)s12672-017-0286-5-e DE-627 ger DE-627 rakwb eng Lillo, M. Angeles verfasserin aut Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer Science+Business Media New York 2017 Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. Cancer Stem Cell (dpeaa)DE-He213 SOX2 Expression (dpeaa)DE-He213 Breast Cancer Stem Cell (dpeaa)DE-He213 Mammary Stem Cell (dpeaa)DE-He213 Breast Stem Cell (dpeaa)DE-He213 Nichols, Cydney aut Seagroves, Tiffany N. aut Miranda-Carboni, Gustavo A. aut Krum, Susan A. aut Enthalten in Hormones and cancer New York, NY [u.a.] : Springer, 2010 8(2017), 2 vom: 27. Feb., Seite 90-99 (DE-627)621547379 (DE-600)2543318-0 1868-8500 nnns volume:8 year:2017 number:2 day:27 month:02 pages:90-99 https://dx.doi.org/10.1007/s12672-017-0286-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 2 27 02 90-99
allfields_unstemmed	10.1007/s12672-017-0286-5 doi (DE-627)SPR027106586 (SPR)s12672-017-0286-5-e DE-627 ger DE-627 rakwb eng Lillo, M. Angeles verfasserin aut Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer Science+Business Media New York 2017 Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. Cancer Stem Cell (dpeaa)DE-He213 SOX2 Expression (dpeaa)DE-He213 Breast Cancer Stem Cell (dpeaa)DE-He213 Mammary Stem Cell (dpeaa)DE-He213 Breast Stem Cell (dpeaa)DE-He213 Nichols, Cydney aut Seagroves, Tiffany N. aut Miranda-Carboni, Gustavo A. aut Krum, Susan A. aut Enthalten in Hormones and cancer New York, NY [u.a.] : Springer, 2010 8(2017), 2 vom: 27. Feb., Seite 90-99 (DE-627)621547379 (DE-600)2543318-0 1868-8500 nnns volume:8 year:2017 number:2 day:27 month:02 pages:90-99 https://dx.doi.org/10.1007/s12672-017-0286-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 2 27 02 90-99
allfieldsGer	10.1007/s12672-017-0286-5 doi (DE-627)SPR027106586 (SPR)s12672-017-0286-5-e DE-627 ger DE-627 rakwb eng Lillo, M. Angeles verfasserin aut Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer Science+Business Media New York 2017 Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. Cancer Stem Cell (dpeaa)DE-He213 SOX2 Expression (dpeaa)DE-He213 Breast Cancer Stem Cell (dpeaa)DE-He213 Mammary Stem Cell (dpeaa)DE-He213 Breast Stem Cell (dpeaa)DE-He213 Nichols, Cydney aut Seagroves, Tiffany N. aut Miranda-Carboni, Gustavo A. aut Krum, Susan A. aut Enthalten in Hormones and cancer New York, NY [u.a.] : Springer, 2010 8(2017), 2 vom: 27. Feb., Seite 90-99 (DE-627)621547379 (DE-600)2543318-0 1868-8500 nnns volume:8 year:2017 number:2 day:27 month:02 pages:90-99 https://dx.doi.org/10.1007/s12672-017-0286-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 2 27 02 90-99
allfieldsSound	10.1007/s12672-017-0286-5 doi (DE-627)SPR027106586 (SPR)s12672-017-0286-5-e DE-627 ger DE-627 rakwb eng Lillo, M. Angeles verfasserin aut Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer Science+Business Media New York 2017 Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. Cancer Stem Cell (dpeaa)DE-He213 SOX2 Expression (dpeaa)DE-He213 Breast Cancer Stem Cell (dpeaa)DE-He213 Mammary Stem Cell (dpeaa)DE-He213 Breast Stem Cell (dpeaa)DE-He213 Nichols, Cydney aut Seagroves, Tiffany N. aut Miranda-Carboni, Gustavo A. aut Krum, Susan A. aut Enthalten in Hormones and cancer New York, NY [u.a.] : Springer, 2010 8(2017), 2 vom: 27. Feb., Seite 90-99 (DE-627)621547379 (DE-600)2543318-0 1868-8500 nnns volume:8 year:2017 number:2 day:27 month:02 pages:90-99 https://dx.doi.org/10.1007/s12672-017-0286-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 2 27 02 90-99
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source	Enthalten in Hormones and cancer 8(2017), 2 vom: 27. Feb., Seite 90-99 volume:8 year:2017 number:2 day:27 month:02 pages:90-99
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topic_facet	Cancer Stem Cell SOX2 Expression Breast Cancer Stem Cell Mammary Stem Cell Breast Stem Cell
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author	Lillo, M. Angeles
spellingShingle	Lillo, M. Angeles misc Cancer Stem Cell misc SOX2 Expression misc Breast Cancer Stem Cell misc Mammary Stem Cell misc Breast Stem Cell Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells
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topic_title	Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells Cancer Stem Cell (dpeaa)DE-He213 SOX2 Expression (dpeaa)DE-He213 Breast Cancer Stem Cell (dpeaa)DE-He213 Mammary Stem Cell (dpeaa)DE-He213 Breast Stem Cell (dpeaa)DE-He213
topic	misc Cancer Stem Cell misc SOX2 Expression misc Breast Cancer Stem Cell misc Mammary Stem Cell misc Breast Stem Cell
topic_unstemmed	misc Cancer Stem Cell misc SOX2 Expression misc Breast Cancer Stem Cell misc Mammary Stem Cell misc Breast Stem Cell
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title_sort	bisphenol a induces sox2 in $ er^{+} $ breast cancer stem-like cells
title_auth	Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells
abstract	Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. © Springer Science+Business Media New York 2017
abstractGer	Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. © Springer Science+Business Media New York 2017
abstract_unstemmed	Abstract Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. © Springer Science+Business Media New York 2017
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title_short	Bisphenol A Induces Sox2 in $ ER^{+} $ Breast Cancer Stem-Like Cells
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However, the concentrations of BPA used in these experiments are far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor (PR)), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft, or the normal mouse mammary gland exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. 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