PROSTATE CANCER--AN IN VIVO MODEL

前列腺癌——体内模型

• 批准号: 2095247
• 负责人: SYDNEY A SHAIN
• 金额: $ 16.52万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2095247
• 关键词: androgens; antibody formation; antisense nucleic acid; cell growth regulation; complementary DNA; disease /disorder model; enzyme linked immunosorbent assay; fibroblast growth factor; gene expression; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory rabbit; laboratory rat; messenger RNA; mitogens; molecular cloning; northern blottings; nucleic acid probes; prostate neoplasms; protein sequence; restriction mapping; southern blotting; testosterone; tissue /cell culture; western blottings

Most prostate cancer initially is androgen responsive. However, maximum androgen blockade, using antoandrogen and GnRH agonist treatment, only moderately increases progression-free survival or median length of survival; suggesting other growth promoters affect cancer cell proliferation. Our studies show that fibroblast-like (FGF-like) growth factors are principal mitogens produced by rat prostate cancer cells and that acidic, aFGF, and basic, bFGF, fibroblast growth factors enhance prostate cancer cell DNA synthesis. The objectives of this proposal are to understand androgen modulation of prostate cancer cell FGF-like mitogen production and FGF-like mitogen modulation of prostate cancer cell proliferation. We propose to address this issue by means of the following specific aims: The goal of aim 1 is to characterize rat prostate and prostate cancer cell FGF transcripts, including analysis for a rat bFGF antisense transcript comparable to that of X. laevis, and to define the relation between prostate cancer cell FGF-like mitogens produced in vitro and in vivo and prototypic aFGF and bFGF. The goal of aim 2 is to use plasmid pKK233-2 to construct expression vectors for generation of rat aFGF and bFGF in E. coli. These mitogens will be used to produce aFGF and bFGF antibodies in rabbits. Antibodies will be used for immunocytochemical localization of FGF-like mitogens in rat prostate cancer tumors, cultured prostate cancer cells, and normal prostate and for ELISA qantification of rat FGF-like mitogen production. Purified rat aFGF and bFGF will be used as standards for ELISA assays and in Western analyses. The goal of aim 3 is to define androgen modulation of prostate cancer cell FGF-like mitogen production in vitro and in vivo. The goal of aim 4 is to test the hypothesis that prostate cancer cell mitogens function in vivo as endocrine polypeptides. The goal of aim 5 is to determine what other mitogens, known to be expressed in prostate tissue, are expressed in rat prostate cancer cells. These studies will provide basic information detailing FGF-like growth factor function in normal and neoplastic prostate and new insight into the interactive roles of androgens and FGFs as modulators of prostate cancer cell proliferation.

最初，大多数前列腺癌是雄激素反应的。 但是，最大 雄激素阻断，使用Antoandrogen和GnRH激动剂治疗，仅 适度增加无进展的生存或中位长度 生存；提示其他增长促进者会影响癌细胞 增殖。 我们的研究表明，成纤维细胞样（类似FGF）生长 因素是由大鼠前列腺癌细胞和 那个酸性，AFGF和碱性BFGF，成纤维细胞生长因子增强 前列腺癌细胞DNA合成。 该提议的目标是 了解前列腺癌细胞FGF样的雄激素调节 有丝分裂原的产生和类似FGF的前列腺癌调节 细胞增殖。 我们建议通过 以下特定目的：目标1的目标是表征老鼠 前列腺和前列腺癌细胞FGF转录物，包括分析 对于大鼠bfgf反义转录本，与X. laevis相当，并且 定义前列腺癌细胞FGF样有丝分裂原之间的关系 在体外和体内以及原型AFGF和BFGF产生。 目标 AIM 2是使用质粒PKK233-2来构建表达向量 大肠杆菌中大鼠AFGF和BFGF的产生。 这些有丝分裂剂将被使用 在兔子中产生AFGF和BFGF抗体。 将使用抗体 用于大鼠前列腺中FGF样有丝分裂原的免疫细胞化学定位 癌症肿瘤，培养的前列腺癌细胞和正常前列腺 用于大鼠FGF样有丝分裂原产生的ELISA量化。 纯化 大鼠AFGF和BFGF将用作ELISA分析的标准和 西方分析。 目标3的目的是定义雄激素调制 前列腺癌细胞在体外和体内产生类似于FGF的有丝分裂原产生。 目标4的目的是检验前列腺癌细胞的假设 有丝分裂剂在体内作为内分泌多肽的作用。 目标5的目标 是确定哪些其他有丝分裂剂，已知在前列腺中表达 组织在大鼠前列腺癌细胞中表达。 这些研究会 提供基本信息详细介绍FGF样生长因子功能 正常和肿瘤前列腺以及对交互式的新见解 雄激素和FGF作为前列腺癌细胞调节剂的作用 增殖。