Stromal-Epithelial Interactions in Development of BPH

描述(由申请人提供)： 我的长期目标是研究良性前列腺增生症(BPH)间质-上皮相互作用的生物学。由于前列腺的发育、生长和肿瘤发生受到基质-上皮细胞串扰的密切调控，明确前列腺上皮细胞与周围基质细胞之间的信号转导通路将有助于我们更好地了解前列腺疾病的正常和异常生物学。我推测，特定间质基因的表达是调节前列腺上皮细胞增殖、细胞死亡和分化的组成部分之一，从而导致成年后的BPH。 Jun家族蛋白是早期的转录因子分子，已被证明通过旁分泌调节来调节间质-上皮相互作用。此外，Jun家族成员蛋白已被证明在泌尿生殖器官的正常发育中发挥着重要作用。间质中不同Jun家族表达之间的平衡可能是间质对前列腺上皮细胞施加最终生存或死亡信号的决定因素之一。 这项建议将解决由含有转基因Jun家族蛋白的基质细胞形成的旁分泌信号是否可以调节上皮细胞增殖、细胞死亡和分化。Jun家族蛋白的间质表达将与已知在前列腺间质-上皮相互作用中重要的信号转导途径有关。这些研究可以提高我们对正常和异常的间质-上皮相互作用的理解，这些相互作用可能导致成年后的BPH。

DESCRIPTION (provided by applicant): My long-term goal is to study the biology of stromal-epithelial interactions in benign prostatic hyperplasia (BPH). Since development, growth and tumorigenesis in the prostate is closely regulated by the stromal-epithelial crosstalk, identifying the signal transduction pathways between prostate epithelial cells and the surrounding stromal cells will enable us to better understand the normal and abnormal biology in prostatic diseases. I hypothesize that expression of particular stromal genes is one of the components that regulates the proliferation, cell death and differentiation of prostatic epithelial cells leading to BPH in adulthood. The Jun-family proteins that are early transcription factor molecules have been shown to regulate stromal-epithelial interactions via paracrine modulation. Moreover, the Jun family member proteins have been shown to play an important role in proper development of the genitourinary organs. The balance between the different Jun-family expression in the stroma may be one of the determinants of the ultimate survival or death signals that the stroma may exert on prostatic epithelial cells. This proposal will address whether paracrine signals form stromal cells with genetically modified Jun-family proteins can regulate epithelial proliferation, cell death and differentiation. Stromal expression of Jun-family proteins will be examined in relation to signal transduction pathways known to be important in prostatic stromal-epithelial interactions. These studies can improve our understanding of normal and abnormal stromal-epithelial interactions that may lead to BPH in adulthood.