Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells

Abstract

Emerging evidence from epidemiological studies suggests a link between environmental chemical exposure and progression of aggressive breast cancer subtypes. Of all clinically distinct types of breast cancers, the most lethal phenotypic variant is inflammatory breast cancer (IBC). Overexpression of epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER) negativity is common in IBC tumor cells, which instead of a solid mass present as rapidly proliferating diffuse tumor cell clusters. Our previous studies have demonstrated a role of an adaptive response of increased antioxidants in acquired resistance to EGFR-targeting drugs in IBC. Environmental chemicals are known to induce oxidative stress resulting in perturbations in signal transduction pathways. It is therefore of interest to identify chemicals that can potentiate EGFR mitogenic effects in IBC. Herein, we assessed in ER-negative IBC cells a subset of chemicals from the EPA ToxCast set for their effect on EGFR activation and in multiple cancer phenotypic assays. We demonstrated that endocrine-disrupting chemicals such as bisphenol A (BPA) and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane can increase EGFR/ERK signaling. BPA also caused a corresponding increase in expression of SOD1 and anti-apoptotic Bcl-2, key markers of antioxidant and anti-apoptotic processes. BPA potentiated clonogenic growth and tumor spheroid formation in vitro, reflecting IBC-specific pathological characteristics. Furthermore, we identified that BPA was able to attenuate the inhibitory effect of an EGFR targeted drug in a longer-term anchorage-independent growth assay. These findings provide a potential mechanistic basis for environmental chemicals such as BPA in potentiating a hyperproliferative and death-resistant phenotype in cancer cells by activating mitogenic pathways to which the tumor cells are addicted for survival.

Source: https://academic.oup.com/carcin/article-abstract/38/3/252/2952402/Bisphenol-A-activates-EGFR-and-ERK-promoting?redirectedFrom=fulltext

Holding Thermal Receipt Paper and Eating Food after Using Hand Sanitizer Results in High Serum Bioactive and Urine Total Levels of Bisphenol A (BPA)

Abstract

Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone’s urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.

Source: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0110509

Does BPA disrupt autophagy in the liver?

Bisphenol A (BPA), which is used in the manufacture of plastic food containers and refillable drinks bottles, dysregulates authophagy-regulated lipid metabolism in hepatocytes, according to new research published in Endocrinology.

Source:http://www.nature.com/nrendo/journal/vaop/ncurrent/full/nrendo.2017.27.html

the BPA pill 

Bisphenol A, commonly known as BPA, is the great unknown threat to western civilization. More dangerous than demographic shifts, Islam, or even the dreaded THOT, it is set to become the most important political issue of our age. At over 6 billion pounds produced per year it is most ubiquitous plasticizer used on earth. It’s xenoestrogens find their way into your body from the of plastic products you use every day. Bisphenol A is in everything, from your plastic bottle of glistening filtered spring water, to the catheter you’ll use once the toxins from BPA turn cells in your prostate cancerous. Did someone hand you a receipt today? Hopefully you had not recently sterilized your hands with that little bottle of congealed rubbing alcohol you have in the car. Ten thousand times more BPA just leeched into your bloodstream because you used hand sanitizer before touching that thermal paper receipt. If that wasn’t already enough, just remember that it’s in your kid’s milk bottle, your toothbrush, your dental implants and fillings, and your Tupperware lunch container that you microwaved earlier. Bisphenol A is It is the cause of your depression, your low T, your man tits. BPA will be the downfall of civilization that no one sees coming.