PROGESTERONE RECEPTORS IN BREAST CANCER

这项建议的目的是研究该法规和 A蛋白(Mr 94,000)和B蛋白(Mr 120,000)的生物活性 人乳腺癌孕激素受体(PR)。我们将使用 孕激素反应性乳腺癌细胞系(原位) 光亲和标记、抗受体抗体和PR基因 探索：a)研究转录和/或后转录 孕激素和孕激素对PR信息的转录调控 雌激素，并评估激素对mRNA和蛋白质周转的影响 比率；b)测定正常和乳腺癌的PR基因拷贝数 PR过度表达的细胞；c)分析处理状态 以及6个不同PR消息频段的5‘和3’端；d) 通过混合选择和混合逮捕翻译显示， 只有B受体或A受体和B受体都能合成 在体外；d)将野生型PR全长cDNAs和cDNAs分别转入 哪些A或B受体翻译起始点已被破坏 通过突变，或结合在一起，是对孕激素的反应所必需的； F)开发研究表达的方法，通过分离受PR调节的 消息，并通过搜索孕激素调节的生长 细胞条件培养液中的抑制因子；g)解决 其中一些研究的临床应用。

The object of this proposal is to study the regulation and the bioactivity of the A-protein (Mr 94,000) and B-protein (Mr 120,000) of human breast cancer progesterone receptors (PR). We will use progestin responsive breast cancer cell lines, in situ photoaffinity labeling, anti-receptor antibodies, and PR cDNA probes to: a) study the transcriptional and/or post- transcriptional regulation of PR messages by progestins and estradiol, and assess hormonal effects on mRNA and protein turnover rates; b) determine PR gene copy number in normal and breast cancer cells where PR are over-expressed; c) analyze the processing state and the 5'- and 3'-termini of six different PR message bands; d) show, by hybrid selection and hybrid arrest translation, whether only B-receptors or both A- and B-receptors can be synthesized in vitro; d) transfect full length wild-type PR cDNA, and cDNAs in which A- or B-receptor translation start sites have been destroyed by mutation, or together, are needed for response to progestins; f) develop methods to study expression, by isolating PR-regulated messages, and by searching for progestin-regulated growth inhibitory factors in cell-conditioned media; g) address the clinical applications of some of these studies.