SMOOTH MUSCLE-EPITHELIAL INTERACTIONS IN PROSTATE CANCER

使用动物和人体模型，这个项目的主要目标是 研究平滑肌(SM)的细胞和分子机制 调节细胞生长和分化的上皮相互作用 正常和恶性前列腺上皮(PRE)。假设是这样的 SM在前列腺中的分化是相互SM&lt；-&gt； 上皮之间的相互作用在维持内环境平衡方面发挥作用 成人前列腺的结构和功能。在前列腺癌发生过程中 SM&lt；-&gt；上皮信号的进行性扰动导致 从去分化的SM细胞中培养出肿瘤间质 积极促进或允许前列腺癌的发生。追寻 这种前列腺瘤的模型，具体目标如下 追踪：(L)分析Pre对SM细胞与肿瘤的应答 斯特尔玛。(2)正常Pre与Pre的差异效应分析 前列腺癌细胞对SM细胞分化的影响。(3) 调节前列环素的旁分泌因子的鉴定与鉴定 生长和SM分化。(4)雄激素生成机制分析 SM分化。(5)基质调节与可逆性分析 上皮性B-钙粘附素。(6)E-钙粘素系统的特性 与Pre细胞体外生长中上皮黏附的相关性 用正常或肿瘤间质细胞来确定是否有影响 Pre中E-钙粘素系统上的基质细胞是通过直接 细胞接触或旁分泌作用分子。(7)逆转或抑制 通过药理药剂减少预粘连。的具体目标 这项研究将通过对组织重组体的分析来检验 活体，转基因小鼠的使用，细胞培养，免疫细胞化学，以及 多种生化和分子方法(RT-PCR、核糖核酸酶保护、 蛋白质印迹、蛋白质纯化和凝胶电泳)。青蛙 拟议的研究预计这项工作将确定新的 有助于区分攻击性和攻击性的诊断标志物 生长缓慢的前列腺癌。此外，这也有可能是 研究将确定一个或多个调控增长的策略， 前列腺癌细胞的分化和侵袭行为。

Using both animal and human models, the main goal of this project is to investigate cellular and molecular mechanisms of smooth muscle (SM)- epithelial interactions which regulate growth and differentiation of normal and malignant prostatic epithelium (PRE). The hypothesis is that SM differentiates in the prostate as a result of reciprocal SM <-> epithelial interactions that play a homeostatic role in maintaining adult prostatic structure and function. During prostatic carcinogenesis progressive perturbation of SM <-> epithelial signaling leads to development of a tumor stroma from dedifferentiated SM cells which either actively promote or permit prostatic carcinogenesis. To pursue this model of prostatic neoplasia, the following specific aims will be pursued: (l) Analysis of response of PRE to SM cells versus tumor stroma. (2) Analysis of differential effects of normal PRE versus prostatic carcinoma cells on differentiation of SM cells. (3) Identification and characterization of paracrine factors regulating PRE growth and SM differentiation. (4) Analysis of androgenic mechanisms of SM differentiation. (5) Analysis of stromal regulation and reversibility of epithelial B-cadherin. (6) Characterization of the E-cadherin system and epithelial adhesion in PRE cells growing in vitro in association with normal or tumor stromal cells to determination whether effects of stromal cells on the E-cadherin system in PRE is mediated via direct cell contact or paracrine acting molecules. (7) Reversal or inhibition of reduced PRE adhesion by pharmacologic agents. The specific aims of this study will be examined through analysis of tissue recombinants in vivo, use of transgenic mice, cell culture, immunocytochemistry, and a variety of biochemical and molecular methods (RT-PCR, RNase protection, Western blot, protein purification, and gel electrophoresis). Frog the proposed studies it is anticipated that the work will identify new diagnostic markers useful for discriminating between aggressive versus slow growing prostatic tumors. In addition, it is possible that this study will identify one or more strategies for regulating the growth, differentiation and)'or invasive behavior of prostatic carcinoma cells.