TCDD elevates erbB2 expression and signaling in T47D cells by reversing serum potentiation of estrogen receptor activity, independent of estrogen levels and enhanced ER down-regulation.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced erbB2 and erbB3 in estrogen receptor (ER) positive T47D (T47D+) cells, but substantially slower than the direct induction of CYP1A1 or CYP1B1. Similar maximum erbB levels were observed in ER- T47D cells or in T47D+ cells cultured in estrogen (E2)-free, defined media (SFM) or serum media with anti-estrogen ICI 182,780. Serum greatly potentiated E2-suppression of erbB expression, which required, at most, 1 pM E2, relative to SFM (20- vs. fourfold). TCDD stimulation (fivefold) was only observed in serum, suggesting that increases arise from reversal of this serum potentiation process (phosphorylation, nuclear co-factors, etc.). ER-degradation was increased by TCDD, but this required high levels of E2 and was independent of serum. E2-hydroxylation is excluded by the lack of effect of excess E2. TCDD enhanced heregulin-stimulated signaling in T47D+ cells, in a parallel manner to erbB2 and erbB3 induction.
Angus
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WG
Department of Pharmacology and Environmental Health Sciences Center, University of Wisconsin, 3770 MSC, 1300 University Avenue, Madison, WI 53706, USA.
Campaigne Larsen
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Jefcoate
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CR
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D020890:Neuregulin-1 / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004958:Estradiol; D004965:Estrogen Antagonists; D004967:Estrogens; D000077267:Fulvestrant; D020890:Neuregulin-1; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D011960:Receptors, Estrogen