Bisphenol A Induces Gene Expression Changes and Proliferative Effects through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts

Pupo, Marco; Pisano, Assunta; Lappano, Rosamaria; Santolla, Maria Francesca; Francesco, Ernestina Marianna De; Abonante, Sergio; Rosano, Camillo

doi:10.1289/ehp.1104526

Cited by 250 publications

(174 citation statements)

References 40 publications

(63 reference statements)

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…In addition, our and other studies have largely demonstrated the involvement of GPER in the stimulatory effects elicited by estrogens in cancer cells and tumor microenvironment (6,(9)(10)(11). Significantly, several studies performed in different cell and animal models have ascertained the role exerted by GPER in certain pathological conditions characterized by oxygen deficiency (30,31,(74)(75)(76)(77)(78).…”

Section: Gper Is Involved In Hypoxia-mediated Signalingmentioning

confidence: 90%

“…As demonstrated for many GPCRs (3,4), the G protein estrogen receptor (GPER, also known as GPR30) may trigger oncogenic signaling (5,6). GPER binds to estrogens, phyto-and xenoestrogens, and also estrogen receptor (ER) antagonists that may act as GPER agonists (7)(8)(9)(10)(11)(12). GPER mediates the activation of a network of transduction pathways; however, the actual role elicited by GPER in tumorigenesis is still controversial.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

Lappano

Rigiracciolo

Marco

et al. 2016

AAPS J

Self Cite

View full text Add to dashboard Cite

Abstract. G protein-coupled receptors (GPCRs) are cell surface proteins mainly involved in signal transmission; however, they play a role also in several pathophysiological conditions. Chemically heterogeneous molecules like peptides, hormones, lipids, and neurotransmitters activate second messengers and induce several biological responses by binding to these seven transmembrane receptors, which are coupled to heterotrimeric G proteins. Recently, additional molecular mechanisms have been involved in GPCR-mediated signaling, leading to an intricate network of transduction pathways. In this regard, it should be mentioned that diverse GPCR family members contribute to the adaptive cell responses to low oxygen tension, which is a distinguishing feature of several illnesses like neoplastic and cardiovascular diseases. For instance, the G protein estrogen receptor, namely G protein estrogen receptor (GPER)/GPR30, has been shown to contribute to relevant biological effects induced by hypoxia via the hypoxia-inducible factor (HIF)-1α in diverse cell contexts, including cancer. Likewise, GPER has been found to modulate the biological outcome of hypoxic/ischemic stress in both cardiovascular and central nervous systems. Here, we describe the role exerted by GPCR-mediated signaling in low oxygen conditions, discussing, in particular, the involvement of GPER by a hypoxic microenvironment.

show abstract

Section: Gper Is Involved In Hypoxia-mediated Signalingmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

Lappano

Rigiracciolo

Marco

et al. 2016

AAPS J

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several studies using animal models and humans have indicated that BPA exposure might produce a broad range of adverse effects, including cancer (Weber Lozada and Keri 2011; Pupo et al 2012), disruption of meiosis and other reproductive anomalies (Allard and Colaiacovo 2010;Hunt et al 2012), impairment of genes that control brain development (Itoh et al 2012), and behavior (Kundakovic et al 2013). In some cases, the phenotypes are accompanied by disrupted expression of DNA methyltransferase 1 and 3A, two enzymes responsible for the incorporation of methyl marks on the DNA (Doherty et al 2010;Itoh et al 2012;Kundakovic et al 2013).…”

Section: Dna Methylation-independent Pathways Of Bpa Toxicitymentioning

confidence: 99%

High Intake of Dietary Sugar Enhances Bisphenol A (BPA) Disruption and Reveals Ribosome-Mediated Pathways of Toxicity

Branco¹,

Lemos²

2014

Genetics

View full text Add to dashboard Cite

Bisphenol A (BPA) is an organic compound to which human populations are ubiquitously exposed. Epidemiological data suggest BPA exposure might be associated with higher rates of diabetes and reproductive anomalies. Health concerns also include transgenerational consequences, but these mechanisms are crudely defined. Similarly, little is known about synergistic interactions between BPA and other substances. Here we show that acute and chronic exposure to BPA causes genome-wide modulation of several functionally coherent genetic pathways in the fruit fly Drosophila melanogaster. In particular, BPA exposure causes massive downregulation of testis-specific genes and upregulation of ribosome-associated genes widely expressed across tissues. In addition, it causes the modulation of transposable elements that are specific to the ribosomal DNA loci, suggesting that nucleolar stress might contribute to BPA toxicity. The upregulation of ribosome-associated genes and the impairment of testis-specific gene expression are significantly enhanced upon BPA exposure with a high-sugar diet. Our results suggest that BPA and dietary sugar might functionally interact, with consequences to regulatory programs in both reproductive and somatic tissues. E XPOSURE to environmental toxins is widespread. It is well documented, for instance, that human populations are commonly exposed to bisphenol A (BPA), bis(2-ethylhexyl) phthalate (DEHP), dioxins, and other organic molecules produced at industrial scales. Toxins might act by modulating epigenetic pathways to change the expression of genes and normal cellular homeostasis and could result in transgenerational consequences. The fast pace at which new compounds are invented and become ubiquitous in the environment poses a challenge to safety assessment. This challenge emerges not only from the large number of compounds to evaluate, but also from the high dimensionality of toxic responses across tissue types and developmental stages. This is further aggravated by the potential for unexpected synergism among toxins in mixtures. Sensitivity might also be strongly dependent on the specific epigenomic features and genetic makeup of an individual (Du et al. 2004).Genomic analyses have uncovered levels of human genetic variation not surmised a few decades ago (e.g., Sudmant et al. 2010). Cost-effective epigenetic and physiological models are needed for (i) addressing tissue-specific responses to toxins, (ii) gaining insights into mechanisms of epigenetic toxicity, and (iii) evaluating the manifestation of these responses across naturally occurring genotypes. In particular, cost-effective models with massive publicly available genetic information (Zwarts et al. 2011; King et al. 2012a,b;Mackay et al. 2012) might allow for genome-wide evaluation of toxic responses and assessment of coexposure outcomes in conjunction with the evaluation of unique individual responses.BPA is one of the most abundantly produced chemicals worldwide, reaching an annual volume .4 million tons (Burridge 2003). Multi...

show abstract

“…12 The high frequency of detection and the rapid metabolism of orally ingested BPA suggests continuous exposure via multiple routes to substantial amounts of BPA. [13][14][15] Many articles have been published on the potentially harmful effects of BPA, including but not limited to its weak estrogenic activity, 3,16 proliferative effects on human breast cancer cells, 17 disruptive effects on both mouse and human pancreatic cells, [18][19][20][21] adverse effects on the fertility and reproductive system of female mice, 4 ability to disrupt fetal mouse prostate and urethra development, 22 and capacity to impair liver function in mice. 23 Many different orthodontic products are used routinely during and after orthodontic treatment, including but not limited to, brackets, adhesives, cements, ligatures, clear aligners, and retainers.…”

Section: Introductionmentioning

confidence: 99%

An investigation into bisphenol-A leaching from orthodontic materials

Kotyk¹,

Wiltshire

2013

The Angle Orthodontist

View full text Add to dashboard Cite

Objective: To quantitatively determine the bisphenol-A (BPA) leached from orthodontic materials during simulated intraoral exposure. Materials and Methods: Samples of orthodontic materials were subjected to simulated abrasion, immersion in artificial saliva, thermal shock via temperature cycling, and simulated intraoral exposure. Sample aliquots were collected for up to 2 weeks after artificial saliva immersion, derivatized, then analyzed for BPA by gas chromatography/mass spectroscopy. Results: Quantifiable amounts of leached BPA were observed from a thermoformed orthodontic retainer material (7.63 mg/g of material) and an orthodontic adhesive (2.75 mg/g of material). BPA leaching was only observed within the first 3 days of artificial saliva immersion. Conclusions: Under the test conditions, BPA was observed to leach from two orthodontic materials. While the quantities of leached BPA were below the reference dose for daily intake, existing data of low-dose effects and medical disorders associated with elevated urinary BPA levels suggest that BPA exposure, and thus the use of the leaching materials identified in this study, should be reduced or eliminated. (Angle Orthod. 2014;84:516-520.)

show abstract

Bisphenol A Induces Gene Expression Changes and Proliferative Effects through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts

Cited by 250 publications

References 40 publications

Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

High Intake of Dietary Sugar Enhances Bisphenol A (BPA) Disruption and Reveals Ribosome-Mediated Pathways of Toxicity

An investigation into bisphenol-A leaching from orthodontic materials

Contact Info

Product

Resources

About