ANDROGEN RECEPTOR EXPRESSION IN PROSTATE DISEASE

局限性前列腺癌的最终治疗是外科手术。 自然和其他形式的治疗，如放射治疗或内分泌治疗 消融术用于复发或转移性疾病。对以下问题的回应 后几种治疗形式仍然不能令人满意。 雄激素-前列腺癌细胞系模型的初步研究 独立前列腺癌明显缺乏AR 表情。这一发现促使人们进行了进一步的回顾分析 提出了选定的几组人的生物行为之间的联系 D期前列腺癌患者AR表达水平的研究 在最初的活组织检查样本中检测到。 目前的提案试图从四个方面探讨这项工作。首先，我们 会尝试确认AR在初始表达之间的关系 活检标本和随后的肿瘤标本的临床行为。 第二，研究AR的分子调控机制 表达，我们将描述前列腺中结合到 AR启动子中的重要功能元件。我们已经隔离了 与AR启动子中的特定序列结合的四个CDNA克隆。我们 将分离出这些cDNA的完整副本并确定 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，我们将研究缺失的分子基础。 AR阴性前列腺癌细胞株中AR的表达第四，我们将 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.