Carcinogenic risk and Bisphenol A exposure: A focus on molecular aspects in endoderm derived glands. (5th December 2017)

• Record Type: Journal Article
• Authors: Cuomo, Danila; Porreca, Immacolata; Cobellis, Gilda; Tarallo, Roberta; Nassa, Giovanni; Falco, Geppino; Nardone, Antonio; Rizzo, Francesca; Mallardo, Massimo; Ambrosino, Concetta
• Is Part Of: Molecular and cellular endocrinology. Volume 457(2017)
• Page Start: 20
• Page End: 34
• Publication Date: 2017-12-05
• Subjects: Bisphenol A -- Thyroid cancer -- Pancreatic cancer -- Prostate cancer -- Nuclear receptors -- Stress/NF-kB pathway; BPA bisphenol A -- NRs nuclear receptors -- NHANES national health and nutrition examination survey -- EFSA european food safety authority -- EDCs endocrine disrupting compounds -- E2 estradiol -- AFP alfa fetoprotein -- ERα estrogen receptor alpha -- ERβ estrogen receptor beta -- ERs estrogen receptors -- MAPKs mitogen-activated protein kinases -- PI3K phosphatidyl-inositol-3-kinase -- NR nuclear receptor -- THR thyroid hormone receptor -- ERR estrogens related receptor -- AR androgen receptor -- PCa prostate adenocarcinoma -- MLL1 mixed lineage leukemia 1 -- H3K4me histone H3 lysine 4 trimethylation -- OECD organization for economic co-operation and development -- AOP adverse outcome pathway -- ESC embryonic stem cell -- TC thyroid cancer -- EZH2 enhancer of zeste homolog 2 -- ATC anaplastic thyroid carcinoma -- HCC hepatocellular carcinoma -- FOXA forkhead box protein A -- AhR aryl hydrocarbon receptor -- ROS oxygen reactive species -- PC pancreatic cancer -- DHT dihydrotestosterone -- RARs retinoic acid receptors -- RXRs retinoid X receptor -- LHR1 liver receptor homologue-1 receptor -- mER membrane estrogen receptor -- PDAC pancreatic ductal adenocarcinoma -- PIN prostatic intraepithelial neoplasia -- PSA prostate specific antigen -- PPAR peroxisome proliferator activated receptor -- PDE4D4 enzyme phosphodiesterase type 4 variant 4; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.01.027
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Epidemiological and experimental evidence associates the exposure to Bisphenol A with the increase of cancer risk in several organs, including prostate. BPA targets different pathways involved in carcinogenicity including the Nuclear Receptors ( i.e. estrogen and androgen receptors), stress regulated proteins and, finally, epigenetic changes. Here, we analyse BPA-dependent carcinogenesis in endoderm-derived glands, thyroid, liver, pancreas and prostate focusing on cell signalling, DNA damage repair pathways and epigenetic modifications. Mainly, we gather molecular data evidencing harmful effects at doses relevant for human risk (low-doses). Since few molecular data are available, above all for the pancreas, we analysed transcriptomic data generated in our laboratory to suggest possible mechanisms of BPA carcinogenicity in endoderm-derived glands, discussing the role of nuclear receptors and stress/NF- k B pathways. We evidence that an in vitro toxicogenomic approach might suggest mechanisms of toxicity applicable to cells having the same developmental origin. Although we cannot draw firm conclusions, published data summarized in this review suggest that exposure to BPA, primarily during the developmental stages, represents a risk for carcinogenesis of endoderm-derived glands. Highlights: Low-dose BPA-dependent carcinogenesis in endoderm-derived glands is described. BPA toxicity mechanisms common to organs from the same germ layer are reported. BPA targets the NRs and stress/NF-kB pathways involved in endoderm carcinogenicity. Developmental exposure to BPA is a risk for carcinogenesis of endoderm glands. In vitro toxicogenomics hints mechanisms of BPA carcinogenicity in endoderm glands.