Different mechanisms contribute to simultaneous inhibition of urokinase and tissue-type plasminogen activators by glucocorticoids in human ovarian carcinoma cells.

Different mechanisms contribute to simultaneous inhibition of urokinase and tissue-type plasminogen activators by glucocorticoids in human ovarian carcinoma cells.
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在人卵巢癌细胞中,不同的机制有助于糖皮质激素同时抑制尿激酶和组织型纤溶酶原激活剂。

DOI:
10.1210/mend-3-6-1006
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发表时间:
1989
影响因子:
--
通讯作者:
B. Littlefield
B. Littlefield
中科院分区:
医学2区
文献类型:
--
作者:
B. Karlan;J. A. Rivero;M. Crabtree;B. Littlefield

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我们实验室之前的研究表明,OVCA 433人卵巢癌细胞对多种标准的糖皮质激素有反应,并且含有高亲和力、可饱和、类固醇特异性糖皮质激素受体。这些细胞分泌哺乳动物纤溶酶原激活物(PA)、尿激酶(uPA)和组织型PA(tPA)。用1 × 10(-7)M地塞米松(Dex)处理OVCA 433细胞4天,导致在1小时内释放到无血清条件培养基中的uPA和tPA的细胞外活性分别降低77%和83%。地塞米松治疗导致细胞外uPA抗原积累率降低71%,如酶联免疫吸附试验所确定的,以及稳态uPA mRNA水平降低73%。相比之下,地塞米松治疗导致细胞外tPA抗原积累率仅下降42%,tPA mRNA水平下降48%;这种下降不足以解释tPA活性下降83%。因此,虽然右旋糖酐诱导的uPA抗原和mRNA水平下降占uPA活性下降的6%,但tPA活性下降的幅度与tPA抗原和mRNA水平下降的幅度之间存在较大差异。OVCA 433细胞产生两种特异性PA抑制剂派-1和派-2。用1 × 10(-7)M Dex处理细胞4天,导致细胞外派-1积累速率增加3.3倍,对派-2积累几乎没有影响。(250字处删节)
Previous studies from our laboratory have demonstrated that OVCA 433 human ovarian carcinoma cells are glucocorticoid responsive by several criteria and contain high affinity, saturable, steroid-specific glucocorticoid receptors. These cells secrete both mammalian plasminogen activators (PAs), urokinase (uPA) and tissue-type PA (tPA). Treatment of OVCA 433 cells with 1 x 10(-7) M dexamethasone (Dex) for 4 days led to 77% and 83% reductions in the extracellular activities of uPA and tPA, respectively, released into serum-free conditioned medium during a 1-h period. Dex treatment led to a 71% decrease in the rate of extracellular uPA antigen accumulation, as determined by enzyme-linked immunosorbent assay, as well as a 73% reduction in steady state uPA mRNA levels. In contrast, Dex treatment led to only a 42% decrease in the rate of extracellular tPA antigen accumulation and a 48% decrease in tPA mRNA levels; such decreases were insufficient to account for the 83% reduction in tPA activity. Thus, while Dex-induced decreases in uPA antigen and mRNA levels accounted for all but 6% of the decrease in uPA activity, a large discrepancy existed between the magnitudes of decreased tPA activity and decreased tPA antigen and mRNA levels. OVCA 433 cells produce both PAI-1 and PAI-2, two specific PA inhibitors. Treatment of cells with 1 x 10(-7) M Dex for 4 days led to a 3.3-fold increase in the rate of extracellular PAI-1 accumulation, with little or no effect on PAI-2 accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
地塞米松在 HTC 肝癌细胞中诱导纤溶酶原激活剂抑制剂。
DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
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发表时间: 1987
期刊: Molecular endocrinology (Baltimore, Md.)
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作者:
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DOI: 10.1126/science.3840278
发表时间: 1985
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影响因子: --
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