7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)90-99
Number of pages10
JournalHormones and Cancer
Volume8
Issue number2
DOIs
StatePublished - Apr 1 2017

Fingerprint

Neoplastic Stem Cells
Breast Neoplasms
MCF-7 Cells
Cell Proliferation
Food and Beverages
bisphenol A
Progesterone Receptors
Human Mammary Glands
Human Body
Heterografts
Estrogen Receptors
Plastics
Estradiol
Estrogens
Breast
Stem Cells
Maintenance
Phosphorylation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research

Cite this

Bisphenol A Induces Sox2 in ER+ Breast Cancer Stem-Like Cells. / Lillo Osuna, Maria Angeles; Nichols, Cydney; Seagroves, Tiffany; Miranda-Carboni, Gustavo; Miranda, Susan.

In: Hormones and Cancer, Vol. 8, No. 2, 01.04.2017, p. 90-99.

Research output: Contribution to journalArticle

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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.",
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AU - Lillo Osuna, Maria Angeles

AU - Nichols, Cydney

AU - Seagroves, Tiffany

AU - Miranda-Carboni, Gustavo

AU - Miranda, Susan

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