Synthetic antiestrogens modulate induction of pS2 and cathepsin-D messenger ribonucleic acid by growth factors and adenosine 3',5'-monophosphate in MCF7 cells.
Synthetic antiestrogens modulate induction of pS2 and cathepsin-D messenger ribonucleic acid by growth factors and adenosine 3',5'-monophosphate in MCF7 cells.
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合成抗雌激素通过生长因子和 3,5-单磷酸腺苷在 MCF7 细胞中调节 pS2 和组织蛋白酶-D 信使核糖核酸的诱导。
DOI：
10.1210/endo.133.2.8344199
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发表时间：
1993
期刊：
影响因子：
4.8
通讯作者：
H. Rochefort
中科院分区：
文献类型：
--
作者：
D. Chalbos;A. Philips;F. Galtier;H. Rochefort
在MCF7人乳腺癌细胞中，抗雌激素4-羟基他莫昔芬和ICI 164,384抑制表皮生长因子（EGF）和胰岛素样生长因子- i （IGF-I）的有丝分裂活性。这些生长因子也刺激组织蛋白酶- d和pS2基因的表达。因此，我们研究了抗雌激素对生长因子诱导pS2和组织蛋白酶- d mRNA的影响。这两种抗雌激素强烈抑制生长因子对pS2的转录诱导。相反，雌二醇和IGF-I或EGF对pS2 mRNA积累有加性作用。生长因子诱导的cathepsin-D也被ICI（164,384）抑制。相比之下，4-羟他莫昔芬对组织蛋白酶- d具有激动作用，对igf -i诱导的mRNA具有加性作用。当用12- o-十四烷醇-13-醋酸酯或8-溴- camp （8-Br-cAMP）代替生长因子时，4-羟基他莫昔芬和ICI 164,384对pS2 （12- o-十四烷醇-13-醋酸酯和8-Br-cAMP）和cathepsin-D （8-Br-cAMP）的诱导作用相似。由于R5020是雌激素诱导pS2和cathepsin-D mRNA的有效抑制剂，因此R5020没有获得抗生长因子活性，因此基于抗雌激素结合和作用于雌激素受体的经典竞争性抑制机制是非常不可能的；2)在石川子宫内膜癌细胞系中，cathepsind基因对雌激素无应答，但经EGF或8-Br-cAMP诱导后，可被抗雌激素抑制；3)细胞内残留雌激素浓度过低，无法诱导雌激素特异性基因的表达。然而，抗雌激素并没有抑制生长因子诱导的所有基因的表达，因为它们对IGF-I诱导的甘油醛-3-磷酸脱氢酶mRNA没有影响。这些结果表明，抗雌激素可以调节一些生长因子诱导基因的转录，并强烈表明这种作用不是由于干扰残留的雌激素。
In MCF7 human breast cancer cells, the antiestrogens 4-hydroxy-tamoxifen and ICI 164,384 inhibit the mitogenic activity of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). These growth factors also stimulate the expression of cathepsin-D and pS2 genes. Therefore, we studied the effects of antiestrogens on growth factor induction of pS2 and cathepsin-D mRNA. The two antiestrogens strongly inhibited the transcriptional induction of pS2 by growth factors. On the contrary, estradiol and IGF-I or EGF had an additive effect on pS2 mRNA accumulation. Growth factor induction of cathepsin-D was also inhibited by ICI 164,384. By contrast, 4-hydroxytamoxifen had an agonist effect on cathepsin-D and an additive effect on IGF-I-induced mRNA. When 12-O-tetradecanoylphorbol-13-acetate or 8-bromo-cAMP (8-Br-cAMP) was used instead of growth factors, similar effects of 4-hydroxytamoxifen and ICI 164,384 were obtained on pS2 (12-O-tetradecanoylphorbol-13-acetate and 8-Br-cAMP) and cathepsin-D (8-Br-cAMP) induction. A mechanism based on the classical competitive inhibition by antiestrogens of estrogen binding and action on the estrogen receptor was very unlikely, as 1) no antigrowth factor activity was obtained with R5020, which was a potent inhibitor of estrogen induction of pS2 and cathepsin-D mRNA; 2) in the Ishikawa endometrial cancer cell line, the cathepsin-D gene is unresponsive to estrogen, but was inhibited by antiestrogen after its induction by EGF or 8-Br-cAMP; and 3) the residual estrogen concentration in cells was too low to induce the expression of estrogen-specific genes. However, antiestrogens did not inhibit the expression of all genes induced by growth factors, as they were without effect on IGF-I induction of glyceraldehyde-3-phosphate dehydrogenase mRNA. These results demonstrate that antiestrogens can modulate the transcription of some growth factor-induced genes and strongly suggest that this effect is not due to interference with residual estrogens.
DOI：
10.1073/pnas.83.8.2496
发表时间：
1986-04-01
影响因子：
11.1
作者：
BERTHOIS, Y;KATZENELLENBOGEN, JA;KATZENELLENBOGEN, BS
通讯作者：
KATZENELLENBOGEN, BS