STERIOD REGULATED EXPRESSION IN THE UTERUS

大多数人乳腺肿瘤含有大量的 雌激素受体，约三分之一的子宫内膜癌， 对某种形式的内分泌治疗有反应。 然而， 激素控制正常或肿瘤细胞中的细胞生长是未知的。 因此，我们建议从根本上调查这一问题。 女性生殖道的基因激活水平。 我们的目标将 建立一个mRNA文库（cDNA文库）， 雌二醇在大鼠子宫内膜细胞中的作用。 除了有 鸟枪法，其中随机响应的mRNA将克隆，我们将 尝试丰富RNA制剂以获取特定编码的信息 对于我们发现由子宫内膜细胞分泌的64 K蛋白， 对雌二醇的反应。 这些cDNA将被用来探测 对雌二醇有反应的各种mRNA的诱导和去诱导 和抗雌激素治疗以及黄体酮给药。 我们将 检查它们在正常发情周期和早期发情周期中的波动， 子宫发育 此外，我们将确定是否有任何这些 cDNA探针与在细胞系中发现的mRNA交叉反应， 来自人子宫内膜癌（HEC-59）。 最后，我们将尝试 确定这些mRNA的染色体DNA序列， 转录。 将用我们的cDNA探测大鼠基因组文库， 寻找含有同源基因组插入物的杂交种。 这些插入件 将绘制地图并进行部分测序， 可能的调节区域，可能负责激素 在这组基因中看到的控制。

The majority of human mammary tumors that contain significant amounts of estrogen receptor, and about one-third of all endometrial carcinomas, respond to some form of endocrine therapy. Yet the mechanism by which hormones control cell growth in either normal or tumor cells is not known. We therefore propose an investigation into this problem at the fundamental level of gene activation in the female reproductive track. Our goal will be to create a library of mRNAs (a cDNA library) that are induced by estradiol in the endometrial cells of rat uterus. In addition to the shotgun approach in which random responsive mRNAs will be cloned, we will attempt to enrich a preparation of RNA for messages that code specifically for the 64K protein that we find to be secreted by endometrial cells in response to estradiol. These cDNAs will then be used to probe the kinetics of induction and deinduction of the various mRNAs that respond to estradiol and antiestrogen treatment and to progesterone administration. We will examine their fluctuation during the normal estrus cycle and during early uterine development. In addition, we will determine whether any of these cDNA probes cross-react with mRNAs that are found in a cell line derived from a human endometrial carcinoma (HEC-59). Finally, we will attempt to identify the chromosomal DNA sequences from which these mRNAs are transcribed. A rat genomic library will be probed with our cDNAs in order to find hybrid phages containing homologous genomic inserts. These inserts will be mapped and partially sequenced with the goal of identifying possible regulatory regions that may be responsible for the hormonal control seen in this set of genes.