ANDROGEN RECEPTOR EXPRESSION IN PROSTATE DISEASE

局限性前列腺癌的决定性治疗是手术治疗， 性质和其他形式的治疗，如放射治疗或内分泌 消融术保留用于复发性或转移性疾病。 响应于 这些后一种形式的治疗仍然不能令人满意。 前列腺癌细胞系雄激素- 独立前列腺癌显示AR显著缺失 表情 这一发现促使回顾性分析，进一步 提出了一种选择性群体的生物学行为之间的联系， D期前列腺癌患者和AR表达水平 在最初的活检标本中检测到。 目前的建议试图从四个方面探讨这项工作。 一是 将尝试确认AR表达与初始 活检标本和肿瘤标本的后续临床行为。 第二，研究AR的分子调控机制 表达，我们将表征前列腺中与前列腺特异性结合的蛋白质。 AR启动子中的重要功能元件。 我们已经分离出 结合AR启动子中确定序列的四个cDNA克隆。 我们 将隔离这些CDNAS的完整拷贝，并确定 它们编码的蛋白质在控制人类AR表达中发挥作用， 前列腺 第三，我们将研究缺乏的分子基础。 AR阴性前列腺癌细胞系中的AR表达。 四是 探索AR表达和细胞生长之间的可能联系。

The definitive therapy of localized prostate carcinoma is surgical in nature and other forms of therapy such as radiotherapy or endocrine ablation are reserved for recurrent or metastatic disease. Response to these latter forms of therapy remains unsatisfactory. Initial studies of prostate carcinoma cells line models of androgen- independent prostate cancer demonstrate a marked absence of AR expression. This finding prompted retrospective analysis that further suggested a link between the biological behavior of selected groups of patients with stage D prostate cancer and the levels of AR expression detected in initial biopsy specimens. The current proposal seeks to explore this work in four ways. First, we will attempt to confirm the relationship between AR expression in initial biopsy specimens and the subsequent clinical behavior of tumor specimens. Second, to investigate the molecular mechanisms controlling AR expression, we will characterize the proteins in prostate that bind to functionally important elements in the AR promoter. We have isolated four CDNA clones that bind to defined sequences in the AR promoter. We will isolate complete copies of these CDNAS and determine what role the proteins they encode play in controlling AR expression in the human prostate. Third, we will examine the molecular basis of the absence of AR expression in AR negative prostate cancer cell lines. Fourth, we will explore possible links between AR expression and cell growth.