REGULATION OF ANDROGEN RECEPTOR ACTIVITY

这项提议的主要目标是获得培训和经验。 在分子生物学技术中，使它们可以用于主要 在他的研究中的研究员实验室。将提供培训 作者：北方大学的弗兰克·弗兰奇和伊丽莎白·威尔逊 在教堂山的卡罗莱纳。指定的实习生将是Jaime Steinsapir， 医学博士，毕业后至少工作一年 在P.I.S实验室进行培训。将进行的研究如下 以下是： 前列腺细胞通过雄激素的存在而对雄激素产生反应 功能性雄激素受体(AR)。这些研究的目标是 确定雄激素和抗雄激素控制AR的机制 正常和肿瘤前列腺细胞的活性和周转。其影响 雄激素戒断对雄激素的影响及mRNA-AR的抗雄激素调控 AR基因的水平和初始转录速率将在 大鼠前列腺腹侧和人前列腺癌细胞(LNCaP)。 雄激素和抗雄激素对小鼠卵巢功能的影响 AR基因上游增强子/启动子偶联的转录活性 通过对AR与启动子序列结合的研究，应确定特异性 参与AR基因自动调节的反应元件。这个 这些结果将有助于进一步了解其分子机制。 雄激素和抗雄激素对AR基因转录的调节 该项目将作为分子使用培训的基础。 激素受体合成和周转的生物学技术。

The major objectives of this proposal are to obtain training and experience in molecular biology techniques so that they can be used in the Principal Investigator's laboratory in his research. The training will be provided by Drs. Frank French and Elizabeth Wilson at the University of North Carolina at Chapel Hill. The designated trainee will be Jaime Steinsapir, M.D., Ph.D. who will work for at least one year after completion of training in the P.I.'s laboratory. The research to be conducted is as follows: Prostate cells are responsive to androgens by virtue of the presence of functional androgen receptors (AR). The goal of these studies is to determine mechanisms by which androgens and antiandrogens control AR activity and turnover in normal and neoplastic prostate cells. The effects of androgen withdrawal on androgen and antiandrogen control of mRNA-AR levels and initial transcription rate of the AR gene will be examined in rat ventral prostate and human prostate cancer cells (LNCaP). The assessment of the effects of androgen and antiandrogens on the transcriptional activity of the AR gene upstream enhancer/promoter coupled with studies on AR binding to promoter sequences should determine specific response elements involved in AR autoregulation of the AR gene. The results will further help to understand the molecular mechanisms of regulation of AR gene transcription by androgens and antiandrogens. This project will be used as a basis for training in the use of molecular biology techniques in hormone receptor synthesis and turnover.