ANDROGEN RECEPTORS IN CANCEROUS PROSTATIC TISSUE

前列腺癌是男性第二常见的癌症， 第三大癌症杀手 病因不明; 然而，它在去势个体中是缺失的，并且许多肿瘤保留了 与正常分化前列腺相似的雄激素依赖性 组织. 很明显，了解类固醇的最大进展 激素在肿瘤中的作用是通过更好地了解其性质， 特定类固醇受体蛋白的生理学。 因此有 需要一种更可靠和特异的方法来研究雄激素受体 在肿瘤组织中。 受体分子的抗体将提供一种 研究癌组织中雄激素受体特性的有用探针。 在上一个赠款期间，我们开发了必要的技术， 从Dunning前列腺肿瘤中纯化雄激素受体。 这些 技术包括与DNA-琼脂糖凝胶的差异结合， 睾酮亲和层析 此外，我们还描述了 受体的一些物理化学和 类固醇结合特性。 我们证明了受体的三种形式： 不与DNA结合的9.1S非转化受体，7.7S 受体-核糖核蛋白复合物和4.4S转化受体， 与DNA结合。 4.4S受体似乎是一个120，000道尔顿的单体 其结合雄激素类固醇和多核苷酸。 其他形式 的受体似乎是由单体与其他 受体相关蛋白或核糖核蛋白。 在当前 我们计划纯化这些受体物种中的每一种， 单克隆抗体的单体亚基和 受体相关蛋白。 通过使用这些抗体，我们将1）映射 去除受体单体上的类固醇和核苷酸结合域 关于N-末端氨基酸，2）表征推定的 与9.1S受体相关的非类固醇结合蛋白，3） 表征与7.7S受体相关的核糖核蛋白，以及4） 确定这些受体相关蛋白是否发挥任何生理作用 调节靶组织中的雄激素受体。 抗体探针 雄激素受体将允许进一步的理化特性， 雄激素调节的前列腺癌组织中的蛋白质。 远程 我们实验室的目标是能够使用这些抗体， 定量雄激素受体并确定其雄激素作用机制 前列腺癌的治疗 这将是一种新的诊断工具， 评估潜在的治疗方案，以遏制这种疾病。

Cancer of the prostate is the second most common cancer in men and the third leading cancer killer. The etiology of the disease is unknown; however, it is absent in castrated individuals, and many tumors retain the property of androgen dependence similar to normal differentiated prostate tissue. It is clear that the greatest progress in understanding steroid hormone action in tumors is through understanding better the properties and physiology of specific steroid receptor proteins. Therefore, there is a need for a more reliable and specific means for studying androgen receptors in tumor tissue. An antibody to the receptor molecule would provide a useful probe for studying the androgen receptor properties in cancer tissue. During the last granting period, we developed the necessary techniques for purifying the androgen receptor from Dunning prostatic tumor. These techniques included both differential binding to DNA-Sepharose and testosterone-affinity chromatography. Furthermore, we characterized the receptor with respect to a number of its physicochemical and steroid-binding properties. We demonstrated three forms of the receptor: a 9.1S nontransformed receptor which does not bind to DNA, a 7.7S receptor-ribonucleoprotein complex and a 4.4S transformed receptor which binds to DNA. The 4.4S receptor appears to be a 120,000 dalton monomer which binds both androgenic steroids and polynucleotides. The other forms of the receptor appear to be composed of the monomer together with other receptor-associated proteins or ribonucleoproteins. In the current proposal we plan to purify each of these receptor species and develop monoclonal antibodies to both the monomer subunit and the receptor-associated proteins. By using these antibodies, we will 1) map out the steroid- and nucleotide-binding domains on the receptor monomer with respect to the N-terminal amino acid, 2) characterize the putative nonsteroid binding proteins associated with the 9.1S receptor, 3) characterize the ribonucleoprotein associated with the 7.7S receptor and 4) determine if these receptor-associated proteins play any physiological role in regulating androgen receptors in target tissues. Antibody probes to the androgen receptor will allow further physicochemical characterization of the protein in androgen regulated prostatic cancer tissues. The long range objective of our laboratory is to be able to use these antibodies to quantitate androgen receptors and determine their mechanism of androgen action in cancerous prostate. This would be a new diagnostic tool for evaluating potential treatment protocols in arresting this disease.