PROGESTERONE RECEPTOR REGULATION IN ENDOMETRIAL CANCER

人类子宫内膜癌实验模型已建立 开发出人类肿瘤在裸体中生长和传代的技术 维持其生化和形态的小鼠 特点。 黄体酮受体已被表征 并从裸鼠生长的肿瘤中部分纯化，并且 单克隆抗体已制备。 这些实验性的 工具以及敏感调节黄体酮的能力 这个实验系统中的受体使我们处于理想的位置 研究纯化后的理化特性 黄体酮受体蛋白，反过来，将充当 与这些改变的特征进行比较的基础 体内黄体酮受体调节过程中的蛋白质。 因此，本提案的具体目标是 1) 研究 人子宫内膜癌 PR 2) 的结构研究 PR结构的调节，3）确定关系 PR 结构和生物反应之间的关系，4) 分析 孕激素下调 PR 的机制。 这些研究 将极大地增进我们对生物学的理解 孕激素对子宫内膜癌的长期作用 本提案的目标。

An experimental model of human endometrial carcinoma has been developed, in which human tumors are grown and passaged in nude mice with maintenance of their biochemical and morphological characteristics. The progesterone receptor has been characterized and partially purified from tumors grown in nude mice, and monoclonal antibodies have been prepared. These experimental tools, and the ability to sensitively modulate the progesterone receptor in this experimental system place us in an ideal position to study the physicochemical characteristics of purified progesterone receptor proteins, which in turn, will serve as the basis for comparison with the altered characteristics of these proteins during the regulation of progesterone receptor in vivo. Therefore, the specific aims of this proposal are 1) to study the structure of human endometrial carcinoma PR 2) to investigate the regulation of PR structure, 3) to determine the relationship between PR structure and biological response and 4) to analyze the mechanism of down regulation of PR by progestins. These studies will significantly advance our understanding of the biology of progestin action in endometrial carcinoma which is the longterm objective of this proposal.