The influence of antiestrogens on the release of plasminogen activator (uPA) by MDA-MB-231 and MCF-7 breast cancer cells.
The influence of antiestrogens on the release of plasminogen activator (uPA) by MDA-MB-231 and MCF-7 breast cancer cells.
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抗雌激素对 MDA-MB-231 和 MCF-7 乳腺癌细胞释放纤溶酶原激活剂 (uPA) 的影响。
DOI：
10.1023/a:1006592809040
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发表时间：
1998
影响因子：
4
通讯作者：
Pento,JT
中科院分区：
文献类型：
--
作者：
Abidi,SM;Howard,EW;Dmytryk,JJ;Pento,JT
已知纤溶酶原激活剂参与乳腺癌的转移扩散。在本研究中，我们研究了抗雌激素[类似物II（1，1-二氯-顺式-2，3-二苯基环丙烷）（AII），ICI-182，780（ICI）和他莫昔芬（TAM）]对雌激素受体（ER）阳性MCF-7（MCF）和ER阴性MDA-MB-231（MDA）人乳腺癌细胞系体外释放uPA的影响。使用固相放射性测定，发现在培养基中的uPA活性从MDA细胞相比，MCF细胞。在固相测定中，使用来自两种细胞系的培养基，氨基己酸（一种特异性纤溶酶抑制剂）使标记底物的降解减少50-60%，因此表明观察到的大部分蛋白水解是由于uPA介导的纤溶酶原产生纤溶酶。在不存在纤溶酶原的情况下，在定量测定或酶谱法中均未检测到酶活性。在MDA细胞中，单独使用或在雌二醇存在下使用的任何抗雌激素都不会改变uPA的释放。相比之下，在MCF细胞中，ICI单独产生最大抑制（40%）的酶释放，而雌二醇单独产生120%的酶活性增加。在MCF培养物中，当与雌二醇共同给药时，每种抗雌激素药物均将酶活性降低至对照水平。底物凝胶酶谱分析显示，尿激酶型PA是两种细胞系释放的PA的主要形式。本研究中使用的所有三种抗雌激素的活性比较表明，ICI是ER阳性MCF细胞中酶活性的最有效抑制剂。© Rapid Science 1998
Plasminogen activators are known to be involved in the metastatic spread of breast cancer. In the present study we examined the effects of antiestrogens [Analog II (1,1-dichloro-cis-2,3-diphenyl cyclopropane) (AII), ICI-182,780 (ICI) and tamoxifen (TAM)], on thein vitrorelease of uPA from estrogen receptor (ER)-positive MCF-7 (MCF) and ER-negative MDA-MB-231 (MDA) human breast cancer cell lines. Using a solid-phase radioassay, uPA activity was found to be higher in the culture medium from MDA cells compared to MCF cells. Aminocaproic acid, a specific plasmin inhibitor, produced a 50-60% reduction in the degradation of labeled substrate, in the solid phase assay, using culture medium from both cell lines, thus indicating that most of the proteolysis observed was due to uPA-mediated plasmin generation from plasminogen. In the absence of plasminogen, the enzyme activity was not detected in either the quantitative assay or by zymography. In MDA cells, uPA release was not altered by any of the antiestrogens used alone or in the presence of estradiol. In contrast, in MCF cells, ICI alone produced maximal inhibition (40%) of enzyme release, while estradiol alone produced a 120% increase in enzyme activity. When co-administered with estradiol, in MCF cultures, each antiestrogen reduced enzyme activity to control levels. Substrate gel zymography revealed that the urokinase-type PA is the predominant form of PA released by both cell lines. Comparison of the activity of all three antiestrogens used in this study indicates that ICI is the most potent inhibitor of enzyme activity in ER-positive MCF cells. © Rapid Science 1998