NEW APPLICATIONS OF THE PROSTATE CANCER MARKER PSA

前列腺癌（CaP）现在是男性的头号癌症， 杀手虽然肿瘤标志物前列腺特异性抗原（PSA） 作为一种革命性的诊断和治疗方法，PSA也定义了CaP的最 独特而紧迫的问题：CaP几乎完全 转移到骨，产生成骨细胞反应， 事实上，这种最初对雄激素敏感的癌症变得独立， 因此会发展并杀人本项目分为三个部分 子项目和技术核心。 第一个项目旨在了解更多关于CaP细胞的机制， 在治疗前后“贩卖”男性骨头。该办法将 需要进行逆转录酶-聚合酶链反应（RT-PCR） 对骨髓抽吸物进行检测，首先检测PSA，然后检测其他几种 前列腺特异性标志物（例如PSM、hK 2）。这次调查将 描述了CaP细胞在骨中随治疗时间的现象学， 提供了对这些骨骼事件机制的深入了解。 第二个项目旨在在实验室中更多地了解 CaP-骨相互作用的机制。方法将是审查 体外和体内研究了CaP细胞中几种因素的影响， “允许”CaP骨植入、生长和/或独特的成骨细胞 反应将检查的因素包括组织蛋白酶K、PSA、hK 2， PSAM、骨形态发生蛋白和尿激酶型纤溶酶原 活化剂。 第三个项目旨在更多地了解 PSA基因的雄激素非依赖性（AI）调节。该办法 为了进一步表征转录结合位点， PSA启动子上的雄激素反应元件，进一步研究 雄激素受体（AR）的配体非依赖性激活机制， 并更详细地研究蛋白质AR和非AR调节剂。这 信息将有助于理解AI的过程。

Carcinoma of the prostate (CaP) is now the #1 cancer in men and its #2 killer. While the tumor marker prostate specific antigen (PSA) has revolutionized diagnosis and therapy, PSA has also defined CaP's most unique and pressing issues: the tendency of CaP to almost exclusively metastasize to bone giving an osteoblastic response, and the inevitability fact that this initially androgen sensitive cancer becomes independent and therefore progresses and kills. The Project is divided into three subprojects and a technical core. The first project seeks to learn more about the mechanisms of CaP cell "trafficking" to bone in men before and after therapies. The approach will entail performing reverse transcriptase-polymerase chain reaction (RT-PCR) assays on bone marrow aspirates initially to PSA and then to several other prostate specific markers (e.g. PSM, hK2). This investigation will describe the phenomenology of CaP cells in bone over time an therapy, and provide insight into the mechanisms for these bone events. The second project seeks to learn in the laboratory more about the mechanisms of CaP-bone interactions. The approach will be to examine in vitro and in vivo the influence of several factors in CaP cells that may "allow" CaP bone implantation, growth, and/or the unique osteoblastic response. The factors will be examined including Cathepsin K, PSA, hK2, PSAM, bone morphogenic proteins, and urokinase-type plasminogen activators. The third project seeks to learn more about the molecular mechanisms of androgen independent (AI) regulation of the PSA gene. The approach will be to characterize further the transcriptional binding sites unrelated to the androgen response elements on the PSA promoter, pursue further the mechanisms of ligand-independent activation of the androgen receptor (AR), and examine in more detail the protein AR and non-AR regulators. This information will help understand the process of AI.