Ashino-Fuse H, Opdenakker G, Fuse A, Billiau A
Proc Soc Exp Biol Med. 1984 Jun;176(2):109-18. doi: 10.3181/00379727-176-41849.
The human Bowes melanoma cell line secretes a plasminogen activator identical to the extrinsic tissue plasminogen activator (EPA) and different from the urokinase-like plasminogen activators mostly found in human tumor lines. In the continuous presence of 100 ng/ml of phorbol 12-myristate 13-acetate (PMA) the 24-hr production of EPA was increased 5.3-fold (average). Preincubation of the cultures for a limited time period (optimally 3 to 6 hr) also resulted in an increase of the subsequent 24-hr production. EPA produced in the presence of PMA was serologically indistinguishable from that produced spontaneously and its molecular weight as defined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and fibrin-agar zymography was the same as that of spontaneously produced EPA. Treatment of the cells with actinomycin D inhibited PMA-induced EPA production. Also, RNA extracted from PMA-treated cells became enriched in mRNA for EPA. It is concluded that PMA acts by enhancing the transcription of the EPA gene. Cell-associated EPA levels were increased, even when tested as early as 3 hr after initiation of the PMA treatment, thus failing to support the view that increased EPA synthesis occurred as a result of depletion of the cellular pool.
人鲍斯黑色素瘤细胞系分泌一种与外源性组织纤溶酶原激活物（EPA）相同的纤溶酶原激活物，与大多数人肿瘤细胞系中发现的尿激酶型纤溶酶原激活物不同。在持续存在100 ng/ml佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）的情况下，EPA的24小时产量平均增加了5.3倍。将培养物预先孵育一段有限的时间（最佳为3至6小时）也会导致随后24小时产量增加。在PMA存在下产生的EPA与自发产生的EPA在血清学上无法区分，并且通过十二烷基硫酸钠（SDS）-聚丙烯酰胺凝胶电泳和纤维蛋白-琼脂酶谱法测定的其分子量与自发产生的EPA相同。用放线菌素D处理细胞可抑制PMA诱导的EPA产生。此外，从PMA处理的细胞中提取的RNA中EPA的mRNA变得富集。结论是PMA通过增强EPA基因的转录起作用。即使在开始PMA处理后3小时就进行检测，细胞相关的EPA水平也会升高，因此不支持增加的EPA合成是由于细胞池耗尽所致的观点。
