REGULATION OF ANDROGEN RECEPTOR ACTIVITY

这项建议的主要目的是获得培训和经验 在分子生物学技术，使他们可以在校长使用 在他的研究中。 将提供培训 由北方大学的弗兰克·弗伦奇和伊丽莎白·威尔逊博士 查佩尔山的卡罗莱纳。 指定的受训者是海梅·斯坦萨皮尔 医学博士，博士在完成后至少工作一年， 在P.I.的训练的实验室。 所要进行的研究是 如下所示： 前列腺细胞对雄激素有反应， 功能性雄激素受体（AR）。 这些研究的目的是 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。 的影响 雄激素戒断对雄激素和mRNA-AR抗雄激素控制的影响 水平和AR基因的初始转录率将在 大鼠腹侧前列腺和人前列腺癌细胞（LNCaP）。 雄激素和抗雄激素药物对卵巢癌的影响 AR基因上游增强子/启动子偶联的转录活性 通过AR与启动子序列结合的研究， 参与AR基因的AR自动调节的反应元件。 的 这些结果将有助于进一步了解 雄激素和抗雄激素对AR基因转录的调节。 该项目将作为培训使用分子生物学的基础。 生物技术在激素受体的合成和周转。

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.