Estrogenic effects of nonylphenol on pS2, ER and MUC1 gene expression in human breast cancer cells-MCF-7.
Many chemicals have recently been discovered to have estrogenic activity, including the surfactant intermediate nonylphenol (NP). It has been well documented that estrogen is a facilitator of human breast cancer development under certain conditions, and environmental estrogens such as NP are currently under intense investigation. Using the expression of pS2 (a trefoil peptide expressed in breast cancer cells), MUC1 (a member of the mucin family) and ER (the human estrogen receptor) genes as estrogen-responsive reporter genes, the effects of estradiol and NP on human breast cancer cells-MCF-7 were studied. In the time course study, the mRNA expressions were detected after NP (10 microM) or estradiol (E2, 0.1 microM) treatments using the RT-PCR technique. The results indicated: (1) NP and E2 induced pS2 mRNA expression after a 2-h exposure and (2) NP induction produced the highest level of MUC1 mRNA after 2 h, which was reduced to only 42% of control at 48 h. E2 treatment resulted in a gradual increase in MUC1 expression over the course of the exposure. The highest level of MUC1 mRNA was at 48 h. This indicates that NP may stimulate MUC1 expression by a different mechanism than E2. (3) NP affected ER expression in the same manner as MUC1. In contrast, E2 stimulated ER expression in a similar manner as pS2; the highest level was at 2 h and expression remained elevated through the 48-h point. NP is an estrogenic compound that alters pS2, MUC1 and ER gene expression in MCF-7 cells. NP may affect MUC1 expression through a different mechanism than E2. The link between aberrant MUC1, PS2 and ER expression and the development of breast cancer also needs to be elucidated through further investigation.
Ren
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L
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA. renl@post.its.mcw.edu
Marquardt
M A
MA
Lech
J J
JJ
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D010636:Phenols / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011506:Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D004968:Estrogens, Non-Steroidal; D018396:Mucin-1; D009363:Neoplasm Proteins; D010636:Phenols; D011506:Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D004958:Estradiol; C025256:nonylphenol