REGULATION OF PROSTATE EPITHELIAL CELL GROWTH

描述(改编自申请人的摘要)：两种疾病 前列腺上皮、良性前列腺增生症(BPH)与前列腺 癌症是美国男性面临的主要健康问题之一。 放松对前列腺上皮细胞增殖的调控是一个中心事件 在良性和恶性前列腺疾病中都有。这样做的目的是 建议了解两种酪氨酸激酶生长因子(S)的作用 家族、它们的配体和相关的结合蛋白以及雄激素 受体在人前列腺上皮细胞有丝分裂调控中的作用 差异化。我们使用了一个特性良好的SV40T抗原家族- 永生化人前列腺上皮细胞(PEC)及其原代培养 人前列腺上皮细胞培养，取自外科手术 标本要达到以下具体目的：(1)确定 胰岛素样生长因子-1与表皮生长的关系 表皮生长因子(EGF)对SV40T永生化人PEC细胞增殖的影响 我们将单独研究生长因子的反应，并将其与 对细胞生长和受体介导的信号转导的影响。 功能意义将通过研究 干扰生长因子受体功能；(2)构建雄激素 这些永生化细胞系的受体阳性亚系 将全长雄激素受体导入这些细胞，以 允许研究EGF和IGF对这些细胞的影响 和无雄激素；(3)构建新的永生化PEC系 一个受可诱导启动子控制的SV40T抗原基因。这将是 允许在没有或存在SV40的情况下研究生长因子的影响 T抗原；以及(4)检测这些细胞的增殖能力。 和/或裸鼠前列腺内的分化。 EGFR、IGFR和雄激素受体系统AS的研究进展 互动网络是开发有效的新技术的关键 治疗前列腺异常生长的方法。

DESCRIPTION (Adapted from the Applicant's Abstract): Two disease of prostatic epithelium, benign prostate hyperplasia (BPH) and prostate cancer, are among the major health problems faced by American men. Deregulation of prostatic epithelial cell proliferation is a central event in both benign and malignant prostatic disease. The objective of this proposal is to understand the role(s) of two tyrosine kinase growth factor families, their ligands and associated binding proteins, and the androgen receptor in control of human prostatic epithelial cell mitogenesis and differentiation. We use a well characterized family of SV40 T antigen- immortalized human prostate epithelial cells (PEC), as well as primary cultures of human prostatic epithelial cells, obtained from surgical specimens to achieve the following specific aims: (1) to determine the effects of insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) on proliferation of SV40 T immortalized human PEC lines. Growth factor responses will be studied individually and in combination of impact on cell growth and receptor mediated signal transduction. Functional significance will be tested by study of the effect of disruption on growth factor receptor function; (2) To construct androgen receptor positive sublines of these immortalized cell lines by transfection of a full length androgen receptor into these cells, to permit study of the impact of EGF and IGF on these cells, in the presence and absence of androgens; (3) To construct new immortalized PEC lines with an SV40 T antigen gene controlled by an inducible promoter. This will permit study of growth factor effects in the absence or presence of SV40 T antigen; and (4) To test the capacity of these cells for proliferation and/or differentiation within the prostate of the athymic nude mice. Investigation of the EGFR, IGFR, and androgen receptor systems as interactive networks is essential for development of effective new treatments for abnormal prostatic growth.