HETEROSPECIFIC CELL/CELL INTERACTIONS IN PROSTATE GROWTH

前列腺生长中的异种特异性细胞/细胞相互作用

• 批准号: 2906026
• 负责人: GERALD R CUNHA
• 金额: $ 24.37万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-15 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2906026
• 关键词: androgens; athymic mouse; benign prostate hyperplasia; cell cell interaction; cell growth regulation; epidermal growth factor; epithelium; estrogens; genetically modified animals; growth factor receptors; hormone regulation /control mechanism; human fetus tissue; insulinlike growth factor; laboratory rat; pharmacokinetics; prostate; reproductive system pharmacology; testicular feminization; tissue /cell culture; transforming growth factors; urinary tract pharmacology

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.

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中的相互作用， 人类前列腺的分化和发病机理，聚焦 专门针对良性前列腺增生（BPH）。 理由 想法是，在老年男性中的延展性丙酰丝组织的新形成 BPH的发病机理是通过基质上皮相互作用发生的，如果 与胎儿前列腺发育中的人不同。 基质上皮 提出相互作用是通过自分泌/旁分泌生长介导的 因素。 这些长期目标将通过检查以下内容来实现 具体目的：（1）雄激素和雌激素反应的表征 在嵌合的人类塑料中，包括确定的动力学 人 - 塑料嵌合前列腺中的雄激素和雌激素反应。 （2） 分析雄激素和雌激素作用的细胞途径 人类前列腺。 这将包括（a）分析的细胞机制 雄激素对人前列腺上皮的作用，（b）细胞分析 雌激素作用对人前列腺上皮的机制，（c）体内 分析睾丸女性中生长因子/生长因子受体 （TFM）/野生型组织重组和（D）生长的体内分析 雌激素受体敲除（ERKO）/野生的因子/生长因子受体 类型组织重组。 （3）生长因子的体内分析 基质上皮相互作用的介体在生长和发展中 人类前列腺上皮专门针对分析 胰岛素样生长因子-1（IGF-1）和EGF受体在生长和 人类前列腺上皮的发展。 （4）分析 正常情况下，不同生长因子家族之间的相互关系 并损害了前列腺上皮生长。 该项目基于 分析由人类组成的新型体内嵌合组织重组 与正常或生长相关的前列腺上皮（Hupre） 因子基因敲除转基因大鼠或小鼠泌尿生殖器间充质（UGM）。 生长因子/受体表达将通过特定物种评估 RT-PCR可以同时且独立地评估基因表达 上皮与基质。 生长因子/受体表达也将是 通过RNase保护，Western Blot，Northern印迹和 免疫细胞化学。 从基本细胞的分析得出的概念 前列腺生长的机制将应用于BPH的发病机理。