ESTROGENIC EFFECTS OF NONYLPHENOL ON PS2, ER AND MUC1 GENE-EXPRESSIONIN HUMAN BREAST-CANCER CELLS-MCF-7

Many chemicals have recently been discovered to have estrogenic activi ty, including the surfactant intermediate nonylphenol (NP). It has bee n well documented that estrogen is a facilitator of human breast cance r development under certain conditions: and environmental estrogens su ch as NP are currently under intense investigation, Using the expressi on of pS2 (a trefoil peptide expressed in breast cancer cells): MUC1 ( a member of the mucin family) and ER (the human estrogen receptor) gen es as estrogen-responsive reporter genes, the effects of estradiol and NP on human boast cancer cells-MCF-7 were studied. In the time course study, the mRNA expressions were detected after NP (10 mu M) or estra diol (E2, 0.1 mu M) treatments using the RT-PCR technique. The results indicated: (1) NP and E2 induced pS2 mRNA expression after a 2-h expo sure and (2) NP induction produced the highest level of MUC1 mRNA afte r 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 t he exposure. The highest level of MUC1 mRNA was at 48 h. This indicate s that NP may stimulate MUC1 expression by a different mechanism than E2. (3) NP affected ER expression in the same manner as MUC1. In contr ast, E2 stimulated ER expression in a similar manner as pS2; the highe st 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 dif ferent mechanism than E2. The link between aberrant MUC1, PS2 and ER e xpression and the development of breast cancer also needs to be elucid ated through further investigation. (C) 1997 Elsevier Science Ireland Ltd.