ANDROGEN RECEPTOR ASSOCIATED PROTEINS IN PROSTATE CANCER

雄激素受体（AR）是核激素受体的一员 家庭，并在正常的发展中发挥核心作用， 前列腺和前列腺癌。 雄激素的观察结果 前列腺癌的消融治疗表明， 通过AR介导对前列腺癌生长至关重要， AR及其相关蛋白的改变可能 导致原发性和雄激素非依赖性前列腺癌。 了解AR调节基因的机制 因此，表达应该提供对异常的洞察， 可能有助于前列腺癌的发展， 未来治疗的可能目标。 最近的报告显示， 核激素受体必须通过直接或间接地 与其他转录因子接触，包括 激活物、阻遏物和调节物，以介导对 转录。 这项工作的主要目标是确定和 表征与AR介导的蛋白质 和/或调节AR对细胞生长的作用。 初步 研究提供的证据表明，AR相关 DNA结合蛋白复合物在AR过程中发挥作用 调节转录。 这项建议是生物化学和 详细描述了这种AR相关蛋白复合物的功能 以确定它如何调节两个人类AR靶点的表达， 前列腺特异性抗原（PSA）和激肽释放酶2（KLK 2）基因。 的 长期目标是定义AR和相关 前列腺癌中的蛋白质，并确定这些蛋白质是否与 蛋白质可以作为开发药物的靶点， 前列腺癌的治疗

The androgen receptor (AR) is a member of the nuclear hormone receptor family and plays a central role in the development of the normal prostate and in prostate cancer. The observations from androgen ablation treatment of prostate cancer have indicated that signals mediated through the AR are critical for prostate cancer growth and that alterations both in the AR and its associated proteins may contribute to primary and androgen independent prostate cancer. Understanding the mechanisms through which the AR regulates gene expression should, therefore, provide insight into abnormalities which may contribute to the development of prostate cancer and provide possible targets for future treatment. Recent reports have shown that nuclear hormone receptors must function by directly or indirectly making contacts with other transcriptional factors which include activators, repressors and modulators to mediate the effects on transcription. The major goal of this work is to identify and characterize the proteins which associate with the AR to mediate and/or modulate the effects of the AR on cell growth. The preliminary studies have provided evidence to demonstrate that an AR associated DNA binding protein complex plays a role in the process of AR regulated transcription. This proposal is to biochemically and functionally characterize this AR associated protein complex in detail to determine how it regulates the expressions of two human AR target genes, prostate specific antigen (PSA) and kallikrein 2 (KLK2). The long term goal is to define interactions between the AR and associated proteins in prostate cancer and determine whether these associated proteins can be targeted for the development useful drugs in the treatment of prostate cancer.