Estradiol preferentially enhances extracellular tissue plasminogen activators of MCF-7 breast cancer cells.
Estradiol preferentially enhances extracellular tissue plasminogen activators of MCF-7 breast cancer cells.
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雌二醇优先增强 MCF-7 乳腺癌细胞的细胞外组织纤溶酶原激活剂。
DOI：
10.1016/s0021-9258(17)42595-6
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Herbert W. Dickerman
中科院分区：
文献类型：
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作者：
Thomas J. Ryan;James I. Seeger;Anand Kumar;Herbert W. Dickerman
MCF-7人乳腺癌细胞分泌两种免疫类型的纤溶酶原激活剂，一种与尿激酶相关，另一种与尿激酶无关。我们现在已经研究了雌激素刺激分泌型纤溶酶原激活物活性是否反映了一种或两种类型的增加。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳酶谱法进行半定量检查，发现对照细胞的条件培养基含有与尿激酶免疫相关的主要激活剂条带（Mr约54，000）和几乎不可辨别的双峰（Mr约64，000和Mr约68，000）。添加雌二醇或更高浓度的睾酮导致双联体活性显著增强，而54 kDa条带不变。64-68-kDa的二联体与针对Bowes黑色素瘤组织纤溶酶原激活物的抗血清呈免疫反应性，但与抗尿激酶抗体不呈免疫反应性。双联体活性的增强与纤维蛋白酶诱导的总分泌型纤溶酶原激活物活性的增加相关。孕酮和地塞米松都没有增加总活性或64-68-kDa的溶解区。适当浓度的雌激素拮抗剂（LY 156758），放线菌素D，或放线菌酮阻断雌二醇和睾酮的变化。因此，MCF-7细胞分泌的组织纤溶酶原激活物的调节似乎是由雌激素受体过程介导的，并且需要持续的RNA和蛋白质合成。
MCF-7 human breast cancer cells secrete two immunologic types of plasminogen activator, one related to urokinase, the other unrelated. We have now examined whether estrogen stimulation of secreted plasminogen activator activity reflects an increase in one or both types. Examined semiquantitatively by sodium dodecyl sulfate-polyacrylamide gel electrophoretic zymography, the conditioned media of control cells were seen to contain a major activator band (Mr approximately 54,000) immunologically related to urokinase and a barely discernible doublet (Mr approximately 64,000 and Mr approximately 68,000). Addition of estradiol or, at much higher concentrations, testosterone led to marked enhancement of doublet activity, while the 54-kDa band was invariant. The 64-68-kDa doublet was immunoreactive with antiserum directed against Bowes melanoma tissue plasminogen activator but not with antiurokinase antibodies. Enhancement of doublet activity was correlated with hormone-induced increases in total secreted plasminogen activator activity. Neither progesterone nor dexamethasone increased total activity or the 64-68-kDa zones of lysis. Estradiol and testosterone alterations were blocked by appropriate concentrations of an estrogen antagonist (LY156758), actinomycin D, or cycloheximide. Regulation of MCF-7 cell-secreted tissue plasminogen activators thus appears to be mediated by an estrogen receptor process and to require sustained RNA and protein synthesis.