REGULATION OF PROSTATE EPITHELIAL CELL GROWTH

描述（改编自申请人的摘要）： 前列腺上皮、良性前列腺增生（BPH）和前列腺 癌症是美国男性面临的主要健康问题之一。 前列腺上皮细胞增殖的失调是一个中心事件 在良性和恶性前列腺疾病中。的目的 一个建议是了解两个酪氨酸激酶生长因子的作用， 家族、其配体和相关结合蛋白，以及雄激素 受体在人前列腺上皮细胞有丝分裂发生中的调控作用， 分化我们使用了一个很好的SV 40 T抗原家族- 永生化的人前列腺上皮细胞（PEC），以及原代 人前列腺上皮细胞的培养物，从外科手术中获得 标本，以实现以下具体目标：（1）确定 胰岛素样生长因子1（IGF-1）和表皮生长的作用 EGF对SV 40 T永生化人PEC系增殖的影响。 将单独研究生长因子反应，并结合以下因素进行研究： 影响细胞生长和受体介导的信号转导。 功能意义将通过研究 生长因子受体功能的破坏;（2）构建雄激素 受体阳性亚系的这些永生化细胞系， 将全长雄激素受体转染到这些细胞中， 允许研究EGF和IGF对这些细胞的影响， （3）构建新的永生化PEC系， 由诱导型启动子控制的SV 40 T抗原基因。这将 允许在不存在或存在SV 40的情况下研究生长因子的作用 （4）检测这些细胞的增殖能力 和/或无胸腺裸鼠前列腺内的分化。 研究EGFR、IGFR和雄激素受体系统， 互动网络是发展有效新闻 治疗前列腺异常生长。

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.