Molecular mechanism study of BPAF-induced proliferation of ERα-negative SKBR-3 human breast cancer cells in vitro/in vivo

Lei, Bingli; Xu, Lanbing; Tang, Qianqian; Sun, Shuming; Yu, Ming; Huang, Yaoyao

doi:10.1016/j.scitotenv.2021.145814

Cited by 9 publications

(26 citation statements)

References 46 publications

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“…TGFB1, MYC, ErbB, BRCA1, EGFR ). Various studies confirm changes in the expression of these genes or proteins upon bisphenol exposure: in breast cancer cell lines, low concentrations of BPAF [ 61 ] and tetrachloro-BPA [ 62 ] enhanced protein expression of c-Myc and cyclin D1, important for cell cycle progression. In mice, this led to an activation of epidermal growth factor receptor (EGFR) and subsequent increases in growth factor expression related to mammary carcinoma [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Different bisphenols induce non-monotonous changes in miRNA expression and LINE-1 methylation in two cell lines

Oldenburg

Fürhacker

Hartmann

et al. 2021

Environmental Epigenetics

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4,4ʹ-Isopropylidenediphenol (bisphenol A, BPA), a chemical substance that is widely used mainly as a monomer in the production of polycarbonates, in epoxy resins, and in thermal papers, is suspected to cause epigenetic modifications with potentially toxic consequences. Due to its negative health effects, BPA is banned in several products and is replaced by other bisphenols such as bisphenol S and bisphenol F. The present study examined the effects of BPA, bisphenol S, bisphenol F, p,pʹ-oxybisphenol, and the BPA metabolite BPA β-d-glucuronide on the expression of a set of microRNAs (miRNAs) as well as long interspersed nuclear element-1 methylation in human lung fibroblast and Caco-2 cells. The results demonstrated a significant modulation of the expression of different miRNAs in both cell lines including miR-24, miR-155, miR-21, and miR-146a, known for their regulatory functions of cell cycle, metabolism, and inflammation. At concentrations between 0.001 and 10 µg/ml, especially the data of miR-155 and miR-24 displayed non-monotonous and often significant dose–response curves that were U- or bell-shaped for different substances. Additionally, BPA β-d-glucuronide also exerted significant changes in the miRNA expression. miRNA prediction analysis indicated effects on multiple molecular pathways with relevance for toxicity. Besides, long interspersed nuclear element-1 methylation, a marker for the global DNA methylation status, was significantly modulated by two concentrations of BPA and p,pʹ-oxybisphenol. This pilot study suggests that various bisphenols, including BPA β-d-glucuronide, affect epigenetic mechanisms, especially miRNAs. These results should stimulate extended toxicological studies of multiple bisphenols and a potential use of miRNAs as markers.

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Section: Discussionmentioning

confidence: 99%

Different bisphenols induce non-monotonous changes in miRNA expression and LINE-1 methylation in two cell lines

Oldenburg

Fürhacker

Hartmann

et al. 2021

Environmental Epigenetics

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“…The stock solution of BPAF dissolved in dimethyl sulfoxide (DMSO, 99.5%, AMRESCO, Radnor, PA, USA) was kept at −20 °C. The source and maintenance of SK-BR-3 cells can be found in our previous study [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

“…The details of experimental design could be found in our previous study [ 24 ]. Briefly, 24 female BALB/c nude mice were purchased from Shanghai Jihui Experimental Animal Feeding Co., Ltd. (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Our previous study observed that BPAF up-regulated the mRNA levels of most targets associated with GPER1-mediated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways in ER-negative human breast cancer SK-BR-3 cells and induced the cell viability [ 24 ]. In vivo study demonstrated that BPAF increased the weight of SK-BR-3 xenograft tumor in nude mice and up-regulated the mRNA levels of most targets related to GPER1-mediated MAPK and PI3K/Akt signaling pathways in SK-BR-3 tumor tissue [ 24 ]. However, after BPAF enter the organism, BPAF can reach various organs of the body through transportation and metabolism, whether BPAF can activate the expression of target genes related to estrogen signaling pathway in main organs and affect the development of these organs in nude mice with SK-BR-3 xenograft tumor is unclear.…”

Section: Introductionmentioning

confidence: 99%

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Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor

Tang

Lei

et al. 2022

IJERPH

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Environmental estrogens can promote the growth, migration, and invasion of breast cancer. However, few studies evaluate adverse health impacts of environmental estrogens on other organs of breast cancer patients. Therefore, the present study investigated the effects of environmental estrogen bisphenol AF (BPAF) on the main organs of female Balb/cA nude mice with SK-BR-3 xenograft tumor by detecting the organ development and gene expression of targets associated with G protein-coupled estrogen receptor 1 (GPER1)-mediated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways in hypothalamus, ovary, uterus, liver, and kidney. The results showed that BPAF at 20 mg/kg bw/day markedly increased the uterine weight and the uterine coefficient of nude mice compared to SK-BR-3 bearing tumor control, indicating that BPAF promoted the growth of uterus due to its estrogenic activity. Additionally, BPAF significantly up-regulated the mRNA relative expression of most targets related to nuclear estrogen receptor alpha (ERα) and GPER1-mediated signaling pathways in the hypothalamus, followed by the ovary and uterus, and the least in the liver and kidney, indicating that BPAF activated different estrogen activity related targets in different tissues. In addition, BPAF markedly up-regulated the mRNA expression of GPER1 in all tested tissues, and the molecular docking showed that BPAF could dock into GPER1. Because gene change is an early event of toxicity response, these findings suggested that BPAF might aggravate the condition of breast cancer patients through exerting its estrogenic activity via the GPER1 pathway in various organs.

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Tetrachlorobisphenol A and bisphenol AF induced cell migration by activating PI3K/Akt signaling pathway via G protein‐coupled estrogen receptor 1 in SK‐BR‐3 cells

Lei

et al. 2022

Environmental Toxicology

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Different subtypes of breast cancer express positively G protein‐coupled estrogen receptor 1 (GPER1). Our previous studies found that tetrachlorobisphenol A (TCBPA) and bisphenol AF (BPAF) significantly promoted SK‐BR‐3 cell proliferation by activating GPER1‐regulated signals. The present study further investigated the effects of TCBPA and BPAF on the migration of SK‐BR‐3 cells and examined the role of phosphatidylinositol 3‐kinase‐protein kinase B (PI3K/Akt) and its downstream signal targets in this process. We found that low‐concentration BPAF and TCBPA markedly accelerated the migration of SK‐BR‐3 cells and elevated the mRNA levels of target genes associated with PI3K/Akt and mitogen‐activated protein kinase (MAPK) signals. TCBPA‐ and BPAF‐induced upregulation of target genes was significantly reduced by GPER1 inhibitor G15, the PI3K/Akt inhibitor wortmannin (WM), and the epidermal growth factor receptor (EGFR) inhibitor ZD1839 (ZD). G15 and WM also decreased cell migration induced by TCBPA and BPAF. The findings revealed that TCBPA and BPAF promoted SK‐BR‐3 cell migration ability by activating PI3K/Akt signaling pathway via GPER1‐EGFR.

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Molecular mechanism study of BPAF-induced proliferation of ERα-negative SKBR-3 human breast cancer cells in vitro/in vivo

Cited by 9 publications

References 46 publications

Different bisphenols induce non-monotonous changes in miRNA expression and LINE-1 methylation in two cell lines

Different bisphenols induce non-monotonous changes in miRNA expression and LINE-1 methylation in two cell lines

Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor

Tetrachlorobisphenol A and bisphenol AF induced cell migration by activating PI3K/Akt signaling pathway via G protein‐coupled estrogen receptor 1 in SK‐BR‐3 cells

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