Stromal-Epithelial Interactions in Development of BPH

BPH 发展中的间质-上皮相互作用

• 批准号: 6599608
• 负责人: ARIA F OLUMI
• 金额: $ 13.13万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6599608
• 关键词: DNA binding protein; athymic mouse; benign prostate hyperplasia; biological signal transduction; cell death; cell differentiation; cell proliferation; cell transplantation; epithelium; fibroblasts; gene expression; male; molecular pathology; pathologic process; prostate; protein structure function; protooncogene; tissue /cell culture

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.

描述（由申请人提供）： 我的长期目标是研究良性前列腺增生（BPH）中基质上皮相互作用的生物学。自从发育以来，前列腺中的生长和肿瘤发生受到基质上皮串扰的密切调节，确定前列腺上皮细胞和周围的基质细胞之间的信号转导途径将使我们能够更好地了解前列腺疾病中的正常和异常生物学。我假设特定基因基因的表达是调节前列腺上皮细胞的增殖，细胞死亡和分化导致BPH成年的组成部分之一。 早期转录因子分子的Jun-family蛋白已被证明可以通过旁分泌调节调节基质上皮相互作用。此外，已显示Jun家庭成员蛋白在适当发展泌尿生殖器官中起着重要作用。基质中不同的6月份表达之间的平衡可能是基质可能在前列腺上皮细胞上施加的最终生存或死亡信号的决定因素之一。 该建议将解决旁分泌信号是否形成具有转基因的6月份蛋白质的基质细胞可以调节上皮增殖，细胞死亡和分化。与已知在前列腺基质上皮相互作用中很重要的信号转导途径有关，将检查jun家庭蛋白的基质表达。这些研究可以提高我们对可能导致成年后BPH的正常和异常的基质上皮相互作用的理解。