Methyl mercury influences growth-related signaling in MCF-7 breast cancer cells.
Environmental contaminants have been shown to alter growth-regulating signaling pathways through molecular mechanisms that are mainly unclear. Here we report that within a narrow concentration range (0.5-1 microM) methyl mercury (MeHg) significantly stimulated growth of MCF-7 cells, induced Ca(2+) mobilization, and activated extracellular signal-regulated kinase (1/2) (Erk1/2). MeHg modulated E(2)-dependent stimulation of growth in a dose-dependent manner, although MeHg neither suppresses nor increases constitutive E(2) metabolism. MeHg demonstrated weak estrogen receptor (ER)-binding ability. However, long preincubation with antiestrogens LY(156,758) and ICI(164,384) decreased MeHg-induced foci formation, Ca(2+) mobilization, and Erk1/2 activation, confirming involvement of ERs. The MeHg-induced increase in [Ca(2+)](i) was observed to coincide with enhanced Erk1/2 phosphorylation. These data suggest that MeHg can significantly modulate the intracellular signaling environment in MCF-7 cells, resulting in a dose-dependent alteration of ER-mediated estrogenic capacity and therefore should be considered as a potential estrogen-disrupting compound.
Sukocheva
Olga A
OA
Signal Transduction Laboratory, Division of Human Immunology, Hanson Institute, Institute of Medical and Veterinary Science, Frome Road, Adelaide, SA 5000, Australia.
Yang
Yi
Y
Gierthy
John F
JF
Seegal
Richard F
RF
D001943:Breast Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008767:Methylmercury Compounds / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D008767:Methylmercury Compounds; D011960:Receptors, Estrogen; D048052:Mitogen-Activated Protein Kinase 3