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.

摘要

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.