HETEROSPECIFIC CELL/CELL INTERACTIONS IN PROSTATE GROWTH

描述 这项研究的长期目标是剖析复杂的机制 激素作用和生长因子系统在生长过程中的相互作用， 人类前列腺癌的分化和发病机制 特别是关于良性前列腺增生症(BPH)。这样做的理由是 有观点认为，老年男性乳腺导管细胞组织的新生 BPH的发病机制类似于间质-上皮相互作用，如果 与胎儿前列腺发育中的不完全相同。间质上皮 相互作用被认为是通过自分泌/旁分泌生长来调节的。 各种因素。这些长期目标将通过审查以下内容来实现 具体目标：(1)雄激素和雌激素反应的特征 在人类和啮齿动物的嵌合体前列腺中，包括测定 人-啮齿动物嵌合前列腺中的雄激素和雌激素反应。(2) 雄激素和雌激素在高血压病中作用的细胞通路分析 人类的前列腺。这将包括(A)分析细胞机制 雄激素对人前列腺上皮的作用(B)细胞分析 雌激素对人前列腺上皮作用的机制，(C)体内 睾丸女性化过程中生长因子/生长因子受体的分析 (D)体内生长分析 雌激素受体敲除中的因子/生长因子受体(ERKO)/野生型 类型组织重组体。(3)体内生长因子分析 基质-上皮细胞相互作用的介体在人卵巢癌生长发育中的作用 人前列腺特异性上皮细胞的作用分析 胰岛素样生长因子-1及其受体在生长发育中的作用 人前列腺上皮的发育。(4)分析了 正常状态下不同生长因子家族间的相互关系 并损害了前列腺上皮的生长。该项目的基础是 一种新型体内人嵌合组织重组蛋白的分析 与正常或生长相关的前列腺上皮(HuPRE)生长 因子敲除转基因大鼠或小鼠尿生殖窦间充质细胞(UGM)。 生长因子/受体的表达将根据物种的具体情况进行评估 逆转录聚合酶链式反应，可以同时和独立地评估基因的表达。 上皮与间质的对比。生长因子/受体的表达也将 通过核糖核酸酶保护、Western印迹、Northern印迹和 免疫细胞化学。从基本元胞的分析中得出的概念 前列腺生长的机制将被应用于BPH的发病机制。

DESCRIPTION The long-term goal of this research is to dissect the complex mechanistic interplay between hormone action and growth factor systems in the growth, differentiation and pathogenesis of the human prostate, focusing specifically on benign prostatic hyperplasia (BPH). The rationale for this idea is that neoformation of ductalacinar tissue in aged men in the pathogenesis of BPH occurs via stromal- epithelial interactions similar, if not identical, to those in fetal prostatic development. Stromal-epithelial interactions are proposed to be mediated via autocrine/paracrine growth factors. These long-term goals will be pursued by examining the following specific aims: (1) Characterization of androgenic and estrogenic response in chimeric human-rodent prostates, including determining the kinetics of androgenic and estrogenic response in human-rodent chimeric prostates. (2) Analysis of the cellular pathways of androgen and estrogen action in the human prostate. This will include (a) analysis of the cellular mechanism of androgen action on human prostatic epithelium, (b) analysis of the cellular mechanism of estrogen action on human prostatic epithelium, (c) in vivo analysis of growth factor/growth factor receptors in testicular feminization (Tfm)/wild type tissue recombinants, and (d) in vivo analysis of growth factor/growth factor receptors in estrogen receptor knockout (ERKO)/wild type tissue recombinants. (3) In vivo analysis of growth factors as mediators of stromal-epithelial interactions in growth and development of human prostatic epithelium focusing specifically on analysis of the role of insulin-like growth factor-1 (IGF-1) and EGF receptor in growth and development of human prostatic epithelium. (4) Analysis of the inter-relationships between different growth factor families during normal and impaired prostatic epithelial growth. The project is based upon analysis of a novel in vivo chimeric tissue recombinant composed of human prostatic epithelium (huPRE) growing in association with normal or growth factor knockout transgenic rat or mouse urogenital sinus mesenchyme (UGM). Growth factor/receptor expression will be assessed by species specific RT-PCR, which can simultaneously and independently assess gene expression in epithelium versus stroma. Growth factor/receptor expression will also be assessed by RNase protection, Western blot, Northern blot and immunocytochemistry. Concepts derived from the analysis of basic cellular mechanisms of prostatic growth will be applied to the pathogenesis of BPH.