ENDOCRINOLOGY AND THE ROLE OF STROMAL GENES IN PROSTATE CANCER

前列腺上皮细胞的生长和分化开始 并通过前列腺基质细胞的雄激素调节介导。 后 雄激素刺激，来自间质细胞的信号直接导管 上皮细胞的形态发生和细胞分化形成腺样 腺泡。 关于雄激素作用的分子机制知之甚少 前列腺基质细胞中。 前列腺癌是一种雄激素依赖性 疾病 基质-上皮相互作用轴的改变是 很可能是前列腺癌。 我们假设前列腺 基质特异性分子途径是内分泌和 前列腺上皮细胞增殖的旁分泌调节， 分化，并且这些途径是雄激素调节的核心 前列腺癌的发生和发展。 为了解决这个假设， 确定关键的分子机制，本提案的具体目标是 围绕前列腺间质基因表达的作用几个方面 前列腺癌的症状 具体地说，我们想研究基质的作用， 和雄激素依赖性基因，如COUP-TF，在启动和 前列腺肿瘤的进展，并确定这些基因的启动子 用于将来在前列腺基质细胞中特异性表达的基因靶向。 我们将使用转基因小鼠，基因特异性敲除（同源 重组）和体外小鼠前列腺重建系统（MPR）， 实现这些目标。 我们希望这些研究的结果将 帮助我们理解间质在前列腺癌发生中的作用。 在 另外，我们希望能找到前列腺肿瘤的基因探针， 作为基因治疗的方法。

The growth and differentiation of prostatic epithelial cells is initiated and mediated through androgen regulation of prostatic stromal cells. Upon stimulation by androgen, signals from stromal cells direct ductal morphogenesis and cytodifferentiation of epithelial cells to form glandular acini. Little is known about the molecular mechanisms of androgen action in prostatic stromal cells. Prostate cancer is an androgen dependent disease. Alterations i the axis of stromal-epithelial interactions are likely in prostatic carcinoma. It is our hypothesis that prostate stromaspecific molecular pathways are fundamental in the endocrine and paracrine regulation of prostatic epithelial cell proliferation and differentiation, and that such pathways are central to androgen regulated prostate cancer initiation and progression. To address this hypothesis and identify key molecular mechanisms, the specific aims of this proposal are centered on the role of prostate stroma gene expression in several aspects of prostate cancer. Specifically, we want to study the role of stromal and androgen dependent genes, such as COUP-TFs, in the initiation and progression of prostate tumors and to define the promoters of these genes for future gene targeting specifically expressed in prostate stroma cells. We will use transgenic mice, gene specific knockout (homologous recombination) and in vitro mouse prostate reconstitution system (MPR) to achieve these goals. We expect results obtained from these studies will help us understanding the role of stroma in prostate carcinogenesis. In addition, we hope to identify gene probe for prostate tumor and eventually devise as method for genetic therapy.