CELL CELL INTERACTIONS IN PROSTATE CANCER

本研究的目的是研究间质上皮细胞的作用， 前列腺癌发生的相互作用。 总的假设是， 致瘤性生长是个体生长过程的总和， 上皮和基质组织中的诱导组织相互作用。 因此，在本发明中， 肿瘤间质细胞的增殖是前列腺增生的关键过程， 致癌作用部分受上皮细胞趋化活性调节 间质细胞。 以相互的方式，增殖和分化 前列腺癌细胞的增殖受基质细胞的调控。 的 这些相互细胞间相互作用的调解者被认为是 生长因子（GF）。 为实现这些目标， 目标将被追求。 (1)在非肿瘤组织中诱导致癌作用 人前列腺肿瘤致瘤性前列腺上皮细胞 基质将根据上皮生长来定义和表征， 细胞凋亡、细胞分化和癌变。 雄激素 人前列腺上皮生长和肿瘤发生的调控 将确定肿瘤基质细胞对上皮细胞（huPRE）的影响。 的 本研究的明确治疗意义将通过以下方式进行检查： 确定前列腺癌的生长是否依赖于 基质细胞增殖。 在互惠的方式，它将是 确定正常前列腺和前列腺增生中的基质生长 肿瘤是由上皮细胞调节的。 (2)增长分析 上皮和基质细胞中的因子/生长因子受体谱 在上皮癌发生的基质诱导期间， 种特异性RT-PCR。 (3)遗传性病变在乳腺癌中的作用 前列腺上皮细胞对前列腺素诱导的敏感性 肿瘤基质细胞的致癌作用将使用p53测定， Rb基因敲除前列腺上皮细胞。 (4)来剖析分子通路 涉及调节生长的胚间-上皮相互作用， 前列腺上皮细胞的分化转基因敲除小鼠将 采用 在这方面，转基因敲除小鼠将被用来检查 基质雌激素受体在前列腺生长中的作用， 分化，生长因子作为上皮细胞的介质的作用 对前列腺基质增殖的影响，以及生长的作用 因子系统作为间质对上皮细胞影响的介质 前列腺增生的原因 这些研究应 定义正常和非正常细胞中的关键细胞和分子途径， 前列腺的肿瘤生长，并应提供生物学 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.