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 并通过雄激素调节前列腺间质细胞。vt.在.的基础上 雄激素的刺激，来自基质细胞的信号直接引导导管 上皮细胞的形态发生和细胞分化形成腺体 阿契尼。对雄激素作用的分子机制知之甚少。 在前列腺基质细胞中。前列腺癌是一种雄激素依赖性疾病。 疾病。间质-上皮相互作用轴的改变是 很可能是前列腺癌。我们的假设是前列腺 间质特异的分子通路在内分泌和 旁分泌对前列腺上皮细胞增殖的调节作用 分化，而且这种途径是雄激素调节的中心 前列腺癌的发生和发展。为了解决这一假设，并 确定关键的分子机制，这项提议的具体目标是 围绕前列腺间质基因表达在几个方面的作用 前列腺癌。具体地说，我们想要研究基质的作用 和雄激素依赖基因，如COUP-TF，在启动和 前列腺癌的进展及这些基因启动子的确定 为将来在前列腺基质细胞中特异表达的基因打靶奠定基础。 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)以 实现这些目标。我们预计从这些研究中获得的结果将 帮助我们了解间质在前列腺癌发生中的作用。在……里面 此外，我们希望发现前列腺癌的基因探针，并最终 设计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.