Estrogenic effect of a series of bisphenol analogues on gene and protein expression in MCF-7 breast cancer cells.
Bisphenols constitute a family of compounds, which includes many substances that have as a common chemical structure two phenolic rings joined together through a bridging carbon. In the present study, we aimed to determine whether several events triggered by 17 beta-estradiol (E(2)) in MCF-7 breast cancer cells were also observed in response to various bisphenol-A (BPA) analogues. We studied the expression of estrogen controlled genes by measuring the induction of pS2 (mRNA and protein) and progesterone receptor (PgR) as well as the expression of a luciferase reporter gene transfected into MVLN cells. These data were compared to the cell proliferation potency and effectiveness as the latest expression of estrogen controlled functions. Bisphenols showed an agonistic effect in all our assays, suggesting that these compounds may act through all the response pathways triggered by the natural hormone. We found differences between the assays in the potency of bisphenols, defined as the minimum concentration required to produce a maximal effect. In the cell proliferation assay, all tested compounds needed a lower concentration than in the other assays to give maximal response. Our results suggest that the polarity and nature of the substituent in the central carbon determines the estrogenic potency. Presence of two propyl chains at the central carbon appears to confer the greatest potency in both gene and protein expression assays.
Rivas
Ana
A
Laboratory of Medical Investigations, School of Medicine, University of Granada, Spain.
Lacroix
Marc
M
Olea-Serrano
Fátima
F
Laíos
Ioanna
I
Leclercq
Guy
G
Olea
Nicolás
N
D001559:Benzhydryl Compounds; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured / Q000187:drug effects; D025521:Tumor Suppressor Proteins; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D008156:Luciferases; D010636:Phenols; D011506:Proteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; C051838:TFF1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds