Stromal-Epithelial Interactions in Development of BPH

BPH 发展中的间质-上皮相互作用

基本信息

批准号：
7408931
负责人：
ARIA F OLUMI
金额：
$ 1.87万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-01 至 2008-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7408931
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

项目摘要

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。由于前列腺的发育、生长和肿瘤发生受到基质-上皮串扰的密切调节，识别前列腺上皮细胞和周围基质细胞之间的信号转导途径将使我们更好地了解前列腺疾病中的正常和异常生物学。我推测特定基质基因的表达是调节前列腺上皮细胞增殖、细胞死亡和分化的成分之一，导致成年期前列腺增生症。作为早期转录因子分子的 Jun 家族蛋白已被证明可以通过旁分泌调节来调节基质-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重要作用。基质中不同Jun家族表达之间的平衡可能是基质可能对前列腺上皮细胞施加的最终生存或死亡信号的决定因素之一。该提案将解决具有转基因 Jun 家族蛋白的基质细胞的旁分泌信号是否可以调节上皮增殖、细胞死亡和分化。将检查 Jun 家族蛋白的基质表达与已知在前列腺基质-上皮相互作用中重要的信号转导途径的关系。这些研究可以提高我们对可能导致成年期良性前列腺增生的正常和异常间质-上皮相互作用的理解。