Novel Prostate Epithelial Cell Lines from Castrated Rats

描述（由申请人提供）：我们从去势大鼠的前列腺上皮中克隆开发了几种具有三种不同生长特征的细胞系，即缓慢生长、中间生长和快速生长。本提案旨在进一步表征和验证这些不同的细胞系。提出了两个具体目标。具体目标1涉及不同细胞系的进一步表征：核型分析、端粒酶测定、对生长促进和生长抑制因子的反应能力、雄激素反应性和致瘤性。具体目标2将检查在雄激素存在或不存在的情况下，整合素和细胞外基质在上皮细胞从基底向管腔形式分化中的作用。虽然雄激素在前列腺上皮细胞中的分子作用已被广泛研究，但对整合素和细胞外基质在前列腺上皮细胞分化中的作用知之甚少。我们的假设是雄激素的作用（至少在分化中）是通过上皮细胞和细胞外基质的粘附分子的相互作用直接或间接介导的。该项目的最终目标是开发特定谱系的前列腺上皮细胞系，其可用作正常和异常状态下前列腺上皮生长和分化的体外模型。

DESCRIPTION (provided by applicant): We have clonally-developed several cell lines with three different growth characteristics, namely, slow growing, intermediate and fast growing, from the prostate epithelium of castrated rats. The present proposal is for further characterization and validation of these different cell lines. Two specific aims are proposed. Specific Aim 1 deals with the further characterization of the different cell lines: karyotyping, telomerase assay, ability to respond to growth-enhancing and growth-inhibitory factors, androgen responsiveness, and tumorigenicity. Specific Aim 2 will examine the role of integrins and extracellular matrix in the differentiation of epithelial cells from basal to luminal forms in the presence or absence of androgens. Although the molecular action of androgen in prostatic epithelial cells has been studied extensively, little is known on the role of integrins and extracellular matrix in differentiation of prostate epithelial cells. It is our hypothesis that androgen action (at least in differentiation) is mediated either directly or indirectly through the interaction of adhesion molecules of the epithelium and the extracellular matrices. The ultimate goal of this project is to develop prostatic epithelial cell lines of specific lineages that could be used as in vitro models for growth and differentiation of the prostate epithelium in both normal and abnormal states.