CELL CELL INTERACTIONS IN PROSTATE CANCER

本研究的目的是研究间质上皮细胞的作用。 前列腺癌发生中的相互作用。总体假设是 致瘤生长是个体生长过程和 上皮和间质组织中的诱导性组织相互作用。因此， 肿瘤间质细胞的增殖是前列腺癌的关键过程 癌变部分受上皮细胞趋化活性的调节 间质上的细胞。以互惠的方式，增殖和分化 前列腺癌细胞的数量受基质细胞的调节。这个 这些细胞间相互作用的介体被认为是 增长因子(GF)。要实现这些目标，具体有以下几点 我们将追求目标。(1)非致癌组织的诱发致癌作用 人前列腺肿瘤致瘤的前列腺上皮细胞(PRE) 间质将根据上皮生长情况进行定义和表征， 细胞凋亡、细胞分化和癌变。雄激素 人前列腺上皮生长与肿瘤发生的调控 肿瘤间质细胞上皮细胞(HuPRE)的数量将被测定。这个 这项研究的明确的治疗意义将由 确定前列腺癌的生长是否依赖于 间质细胞增殖。以互惠的方式，它将是 确定正常前列腺和前列腺癌的间质生长 肿瘤是由上皮细胞调控的。(2)增长分析 上皮细胞和基质细胞中因子/生长因子受体的分布 在间质诱导上皮细胞癌变的过程中， 种属特异性RT-PCR。(3)遗传损伤在糖尿病发病中的作用 前列腺上皮细胞对丙二醛诱导的敏感性 肿瘤间质细胞的致癌作用将使用P53和 Rb基因敲除的前列腺上皮。(4)分子途径的解剖 涉及调节生长和上皮细胞的间质-上皮相互作用 前列腺上皮转基因基因敲除小鼠的分化 使用。在这方面，转基因基因敲除小鼠将被用于检测 间质雌激素受体在前列腺生长和发育中的作用 分化、生长因子在上皮细胞分化中的中介作用 对前列腺间质增殖的影响，以及生长的作用 因子系统在上皮间质作用中的中介作用 前列腺生长过程中的增殖。这些研究应该 定义关键的细胞和分子通路 前列腺的致瘤性生长，应提供生物学上的 新的治疗策略的基础。

The goal of this research is to study the role of stromal-epithelial interactions in prostatic carcinogenesis. The overall hypothesis is that tumorigenic growth is the sum of individual growth processes and inductive tissue interactions inepithelial and stromal tissues. Thus, proliferation of tumor stromal cells is a key process in prostatic carcinogenesis, which is in part regulate by tropic activity of epithelial cells on stroma. In reciprocal fashion, proliferation and differentiation of prostatic carcinoma cells is regulated by stromal cells. The meddiators of these reciprocal cell-cell interactions are proposed to be growth factrors (GF). To achieve these goals the following specific aims will be pursued. (1) Induction of carcinogenesis in non- tumorigenic prostatic epithelial cells (PRE) by human prostatic tumor stroma willbe defined and characterized in terms of epithelial growth, apoptosis, and cytodifferentiation and carcinogenesis. Androgenic regulationof epithelial growth and tumorigenesis in human prostatic epitheluim (huPRE) by tumor stromal cells will be determine. The clear therapeutic implication of this study will be examined by determine whether growth of prostatic carcinomas is dependent upon proliferationof stromal cells. In reciprocal fashion it will be determined whether stromal growth in normal prostate and prostaic tumors is regulated by epithelial cells. (2) Analysis of the growth factor/growth factor receptor profile in epithelial and stromal cells during stromal induction of epithelial carcinogenesis will be pursued by species specific RT-PCR. (3) The role of genetic lesion in the susceptibility of prostatic epithelial cells to the induction of carcinogenesis by tumor stromal cells will be determined using p53 and Rb knockout prostatic epithelium. (4) to dissect molecular pathways involved instromal-epithelial interactions regulating growth and differentiation of prostatic epithelium transgenic knockout mice will be used. In this regard transgenic knockout mice will beused to examine the role of stromal estrogen receptors in prostatic growth and differentiation, the role of growth factors as mediators of epithelial effects on stromal proliferation in the prostate, and the role of growth factor systems as mediators of stromal effects on epithelial proliferation during growth of the prostate. These studies should define critical cellular and molecular pathways in both normal and tumorigenic growth of the prostate, and should provide the biological basis of new therapeutic strategies.