GENE REGULATION IN TERATOCARCINOMA AND EMBRYONIC CELLS

纤溶酶原激活剂是丝氨酸蛋白酶，其已经参与了纤溶酶原激活剂的合成。 各种各样的正常和异常过程。 提出的实验 解决了两个关于这些酶的广泛问题： 组织纤溶酶原激活物（tPA）的控制，以及什么是 tPA和尿激酶型纤溶酶原激活剂（uPA）的各自作用。 将在F9畸胎癌细胞中研究tPA合成的调节， 该酶的生产可以通过操作 培养条件。 tPA可以反馈抑制其自身 还将通过经典技术在这些细胞中检查合成， 阿托伐他汀介导的诱变，随后转染， 表达特定修饰的酶。 的致瘤特性 还将测定产生这些修饰的tPA的F9细胞。 在大鼠卵巢中，颗粒细胞产生tPA，卵泡膜细胞产生tPA。 uPA。 对于这两种细胞，酶的合成在排卵时达到最大 并由促性腺激素诱导。 该系统将用于体内和体内 体外研究两种酶在排卵过程中的作用 过程 tPA可能有助于降解卵泡 蛋白聚糖，并且蛋白聚糖可以刺激tPA的活性， 将被审查。

Plasminogen activators are serine proteases that have been implicated in a wide variety of normal and abnormal processes. The experiments proposed address two broad questions concerning these enzymes: how is the synthesis of tissue plasminogen activator (tPA) controlled, and what are the respective roles for tPA and the urokinase-type plasminogen activator (uPA). Regulation of tPA synthesis will be studied in F9 teratocarcinoma cells, in which enzyme production can be conveniently controlled by manipulation of the culture conditions. The fact that tPA can feedback inhibit its own synthesis will also be examined in these cells by classical techniques and oligonucleotide-mediated mutagenesis followed by transfection and expression of specifically modified enzymes. The tumorigenic properties of F9 cells producing these modified tPAs will also be determined. In the rat ovary, granulosa cells produce tPA and thecal cells produce uPA. With both cells, enzyme synthesis is maximal at the time of ovulation and is induced by gonadotropins. This system will be used in vivo and in vitro to investigate the function of the two enzymes in the ovulatory process. The possibility that tPA is instrumental in degrading follicular proteoglycans, and that proteoglycans can stimulate the activity of tPA, will be examined.