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.
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.
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TCDD 通过逆转雌激素受体活性的血清增强作用来提高 T47D 细胞中 erbB2 的表达和信号传导，与雌激素水平无关并增强 ER 下调。
DOI：
10.1016/s0303-7207(00)00337-3
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发表时间：
2000
影响因子：
4.1
通讯作者：
Jefcoate,CR
中科院分区：
文献类型：
--
作者：
Angus,WG;CampaigneLarsen,M;Jefcoate,CR
2，3，7，8-四氯二苯并-对-二恶英（TCDD）诱导雌激素受体（ER）阳性的T47 D（T47 D+）细胞中的erbB 2和erbB 3，但明显慢于直接诱导CYP 1A 1或CYP 1B 1。在不含雌激素（E2）的成分确定培养基（SFM）或含抗雌激素ICI 182，780的血清培养基中培养的ER− T47 D细胞或T47 D+细胞中观察到类似的最大erbB水平。血清极大地增强了E2对erbB表达的抑制，这最多需要1 pM E2，相对于SFM（20- vs. 4倍）。仅在血清中观察到TCDD刺激（5倍），表明增加是由于血清增强过程（磷酸化、核辅因子等）逆转所致。ER-降解增加TCDD，但这需要高水平的E2，是独立的血清。E2-羟基化由于缺乏过量E2的影响而被排除。TCDD增强heregulin刺激的信号在T47 D+细胞，在平行的方式erbB 2和erbB 3诱导。
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 E2and 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.