title: Bisphenol A and its derivatives tetrabromobisphenol A and tetrachlorobisphenol A induce apelin expression and secretion in ovarian cancer cells through a peroxisome proliferator-activated receptor gamma-dependent mechanism.
abstract: Epidemiological studies have reported that humans have detectable levels of not only bisphenol A (BPA), but also its halogenated derivatives tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA), in the serum. Our previous study showed that BPA promotes ovarian cancer progression by directly inducing cell proliferation and migration or by indirectly increasing leptin receptor expression, which creates more binding sites for leptin. In this study, we examined the expression of apelin and its receptor in non-cancer and cancer cell lines derived from the human ovary, and further explored whether the expression of apelin and its receptor is modulated by BPA and its derivatives. We found that the apelin receptor expression level was higher in epithelial cancer cells than in granulosa tumour cells, whereas the reverse was true for apelin expression and secretion. BPA, TBBPA and TCBPA at low nanomolar concentrations increased apelin expression and secretion in the epithelial ovarian cancer cell line OVCAR-3, which involved the peroxisome proliferator-activated receptor γ but not oestrogen receptors. We also found evidence that secreted apelin acts as a mitogenic factor in OVCAR-3 cells, and that BPA intensifies its activity. Taken together, our results suggest that BPA and its derivatives induce ovarian cancer cell progression by up-regulating apelin, which acts as a mitogenic factor in these cells.
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland, Poland. Electronic address: marta.hoffmann@doctoral.uj.edu.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland, Poland. Electronic address: elzbieta.fiedor@doctoral.uj.edu.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Fiedor
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland, Poland. Electronic address: anna.ptak@uj.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Ptak
mesh_terms: D000073861:Apelin; D001559:Benzhydryl Compounds / Q000633:toxicity*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002733:Chlorophenols / Q000633:toxicity*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000098826:Bisphenol A Compounds
chemical_list: D000073861:Apelin; D001559:Benzhydryl Compounds; D002733:Chlorophenols; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D010636:Phenols; D011075:Polybrominated Biphenyls; D011960:Receptors, Estrogen; D054411:Receptors, Leptin; C115436:APLN protein, human; C041181:tetrachlorodian; C020806:tetrabromobisphenol A; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Apelin; Bisphenol A; Ovarian cancer; PPARγ; Tetrabromobisphenol A; Tetrachlorobisphenol A