REGULATION OF PROSTATE EPITHELIAL CELL GROWTH

前列腺上皮细胞生长的调节

• 批准号: 2882799
• 负责人: JOY Laurin WARE
• 金额: $ 16.36万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-18 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2882799
• 关键词: androgen receptor; androgens; athymic mouse; binding proteins; cell differentiation; cell growth regulation; cell line; cell proliferation; epidermal growth factor; growth factor receptors; human tissue; insulinlike growth factor; prostate disorder; transfection

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.

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 (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失调是一个中心事件 良性和恶性前列腺疾病。此举的目的 提案是了解两种酪氨酸激酶生长因子的作用 家族，它们的配体和相关的结合蛋白，以及雄激素 控制人前列腺上皮细胞有丝分裂的受体 差异化。我们使用一个特征明确的 SV40 T 抗原家族 - 永生化人前列腺上皮细胞（PEC）以及原代细胞 人前列腺上皮细胞培养物，从手术中获得 标本达到以下具体目的：（1）确定 胰岛素样生长因子 1 (IGF-1) 和表皮生长的影响 因子 (EGF) 对 SV40 T 永生化人 PEC 系增殖的影响。 生长因子反应将单独研究并结合 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效果来检验 破坏生长因子受体功能； (2)构建雄激素 这些永生化细胞系的受体阳性亚系 将全长雄激素受体转染到这些细胞中，以 允许研究 EGF 和 IGF 在存在的情况下对这些细胞的影响 以及缺乏雄激素； (3)构建新的永生化PEC系 由诱导型启动子控制的 SV40 T 抗原基因。这将 允许研究在不存在或存在 SV40 的情况下生长因子的影响 T抗原； (4) 测试这些细胞的增殖能力 和/或无胸腺裸鼠前列腺内的分化。 EGFR、IGFR 和雄激素受体系统的研究 互动网络对于开发有效的新产品至关重要 治疗前列腺异常生长。