Effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin, 12‐O‐tetradecanoylphorbol‐13‐acetate and 17β‐estradiol on estrogen receptor regulation in MCF‐7 human breast cancer cells
Effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin, 12‐O‐tetradecanoylphorbol‐13‐acetate and 17β‐estradiol on estrogen receptor regulation in MCF‐7 human breast cancer cells
复制标题
2,3,7,8-四氯二苯并-对二恶英、12-O-十四烷酰佛波醇-13-乙酸酯和17β-雌二醇对MCF-7人乳腺癌细胞雌激素受体调节的影响
DOI：
--
复制
发表时间：
1996
影响因子：
4
通讯作者：
D. Spink
中科院分区：
文献类型：
--
作者：
J. Gierthy;B. C. Spink;H. Figge;B. Pentecost;D. Spink
2,3,7,8 -四氯二苯并对二恶英（TCDD）具有显著的抗雌激素活性。为了进一步阐明雌激素受体（ER）调节在这一反应中的作用，我们研究了MCF‐7人乳腺癌细胞暴露于TCDD对ER mRNA水平的影响，使用RNase保护实验，使用ER免疫细胞化学实验（ER‐ICA）对ER积累的影响，以及在饱和17β‐雌二醇（E2）条件下通过竞争结合实验对ER功能的影响。我们将E2和TPA进行了比较研究，因为已知这两种化合物都能抑制内质网的表达。我们的研究结果表明，1 nM E2和100 nM TPA在暴露后4小时就能抑制ER mRNA水平，72小时后分别抑制对照组水平的33.6%和16.5%。相比之下，10 nM TCDD对ER mRNA水平没有显著影响。1 nM E2和100 nM TPA处理72 h后，ER - ICA观察到阳性染色减少50%以上，而10 nM TCDD处理仅减少11%。在饱和条件下（10 nM E2），全细胞中[3H]E2的特异性结合在暴露于100 nM TPA的培养物中减少了50%，尽管暴露于10 nM TCDD的培养物对结合没有影响。相比之下，在暴露于10 nM TCDD 72小时的MCF - 7细胞中，使用过饱和的1 nM [3H]E2的特异性结合被抑制了49%。这种抑制被5 μM α -萘黄酮处理1小时所抑制，这抑制了TCDD诱导的、P450介导的、E2代谢和随后的E2消耗。综上所述，TPA和E2能有效下调内质网的表达，而TCDD在抗雌激素条件下对MCF - 7细胞内的总内质网水平几乎没有影响，因此TCDD对MCF - 7细胞内雌激素活性的抑制可能不需要内质网调节。©1996 Wiley‐Liss, Inc。
2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) exhibits remarkably potent antiestrogenic activity. To further elucidate the role of estrogen receptor (ER) regulation in this response, we examined the effects of exposure to TCDD in MCF‐7 human breast cancer cells on ER mRNA levels by using an RNase protection assay, on ER accumulation by using an ER immunocytochemical essay (ER‐ICA), and on ER function by competitive binding assays under conditions of saturating 17β‐estradiol (E2). Comparative studies were conducted with E2 and 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), as both compounds are known to suppress ER expression. Our results indicate that 1 nM E2 and 100 nM TPA both suppress ER mRNA levels as early as 4 h after exposure and to 33.6% and 16.5% of control levels, respectively, after 72 h. In contrast, no significant effect on ER mRNA levels was attributed to exposure to 10 nM TCDD. A greater than 50% reduction in positive staining was observed by ER‐ICA after 72 h exposure to 1 nM E2 and to 100 nM TPA, while only an 11% reduction in positive staining was observed with 10 nM TCDD. Specific binding of [3H]E2 under saturating conditions (10 nM E2) in whole cells was reduced by 50% in cultures exposed to 100 nM TPA, although no effect on binding was observed with exposure to 10 nM TCDD. In contrast, specific binding using subsaturating 1 nM [3H]E2 was depressed by 49% in MCF‐7 cells exposed to 10 nM TCDD for 72 h. This depression was inhibited by a 1‐h treatment with 5 μM α‐naphthoflavone, which inhibits TCDD‐induced, P450‐mediated, E2 metabolism, and subsequent E2 depletion. In conclusion, while TPA and E2 effectively down‐regulate ER expression, TCDD, under antiestrogenic conditions, has little if any effect on total ER levels in MCF‐7 cells, and thus ER modulation is probably not necessary for the suppression of estrogenic activity in MCF‐7 cells by TCDD. © 1996 Wiley‐Liss, Inc.
登录
查看更多内容
2,3,7,8-四氯二苯并-对二恶英和视黄酸在 MCF-7 人乳腺癌细胞中的相互作用。
影响因子：
3.8
作者：
Lu,Y;Wang,X;Safe,S
通讯作者：
Safe,S
影响因子：
11.2
作者：
M. Harris;T. Zacharewski;S. Safe
通讯作者：
M. Harris;T. Zacharewski;S. Safe
DOI：
10.1080/15287399409531856
发表时间：
1994-04
期刊：
Journal of toxicology and environmental health
影响因子：
--
作者：
D. Spink;J. Johnson;S. Connor;K. Aldous;J. Gierthy
通讯作者：
D. Spink;J. Johnson;S. Connor;K. Aldous;J. Gierthy
影响因子：
--
作者：
Hyeseong Cho;Peter A. Ng;B. Katzenellenbogen
通讯作者：
Hyeseong Cho;Peter A. Ng;B. Katzenellenbogen
α-萘黄酮作为 2,3,7,8-四氯二苯并-对二恶英诱导的 CYP1A1 基因表达抑制剂的作用机制。
影响因子：
3.9
作者：
Merchant,M;Arellano,L;Safe,S
通讯作者：
Safe,S