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
基本信息
- 批准号:6177961
- 负责人:
- 金额:$ 25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 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
项目摘要
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,
生长中激素作用和生长因子系统之间的相互作用,
分化和发病机制的人前列腺,重点
特别是良性前列腺增生症(BPH)。 这样做的理由
想法是在老年男性中导管腺泡组织新形成,
BPH的发病机制通过基质-上皮相互作用发生,如果
与胎儿前列腺发育中的不完全相同。 间质上皮
提出了通过自分泌/旁分泌生长介导的相互作用
因素 为实现这些长期目标,将审查以下方面:
具体目的:(1)雄激素和雌激素反应的表征
在嵌合的人-啮齿动物前列腺中,包括测定
人-啮齿动物嵌合体前列腺的雄激素和雌激素反应。 (二)
雄激素和雌激素在卵巢癌中作用的细胞通路分析
人类前列腺。 这将包括(a)分析细胞机制
雄激素对人前列腺上皮细胞的作用,(B)对细胞的分析
雌激素对人前列腺上皮作用机制,(c)体内
睾丸女性化中生长因子/生长因子受体的分析
(Tfm)/野生型组织重组体,和(d)生长的体内分析
雌激素受体敲除(ERKO)/野生型因子/生长因子受体
型组织重组体。 (3)生长因子的体内分析,
基质-上皮相互作用的介质在生长和发育中的作用
人前列腺上皮细胞,特别关注分析
胰岛素样生长因子-1(IGF-1)和EGF受体在生长和
人前列腺上皮的发育。 (4)分析
正常情况下不同生长因子家族之间的相互关系
以及前列腺上皮生长受损。 该项目基于
分析由人源性嵌合体组成的新型体内嵌合组织重组体
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(UGM)。
生长因子/受体表达将通过种属特异性
RT-PCR,它可以同时和独立地评估基因表达,
上皮与间质。 生长因子/受体的表达也将是
通过RNA酶保护、蛋白质印迹、北方印迹和
免疫细胞化学 从基本细胞分析中得出的概念
前列腺生长的机制将应用于BPH的发病机制。
项目成果
期刊论文数量(0)
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{{ truncateString('GERALD R CUNHA', 18)}}的其他基金
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:
2713463 - 财政年份:1997
- 资助金额:
$ 25万 - 项目类别:
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:
2018210 - 财政年份:1997
- 资助金额:
$ 25万 - 项目类别:
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 - 财政年份:1997
- 资助金额:
$ 25万 - 项目类别:
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:
6381351 - 财政年份:1997
- 资助金额:
$ 25万 - 项目类别:
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