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 (E-2)-free, defined media (SFM) or serum media with anti-estrogen ICI 182,780. Serum greatly potentiated E-2-suppression of erbB expression, which required, at most, 1 pM E-2, 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 E-2 and was independent of serum. E-2-hydroxylation is excluded by the lack of effect of excess E-2. TCDD enhanced heregulin-stimulated signaling in T47D(+) cells, in a parallel manner to erbB2 and erbB3 induction. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.