Characterization of a Growth Inhibitory Activity from Urogenital Sinus

在前列腺器官发生过程中，胎儿泌尿生殖窦间充质诱导并指导偶联上皮的表型分化。这导致腺管和腺泡的形成，典型的成人腺体形态。Rowley博士实验室以前的研究使用胎儿泌尿生殖窦的器官培养来鉴定间质中潜在的生长和分化调节因子。这些研究已经从泌尿生殖窦器官培养和衍生的间充质细胞系的条件培养基中确定了生长抑制因子。此外，生长抑制活性影响膀胱和前列腺上皮细胞系，表明这种活性可能影响细胞分化。负责活性的蛋白质已被纯化到接近均匀性。该项目的长期目标是了解这个被称为UGIF的因子在器官发生过程中间充质上皮相互作用中的基本作用。这里提出的研究的直接目标是：开发特异性UGIF蛋白的抗体和寡核苷酸探针；分离和克隆编码UGIF和的cDNA；确定UGIF在体内的时空表达模式。本研究将为确定UGIF作为体内调节因子的潜在意义以及其在间充质上皮相互作用和相关器官发生的基本机制中的具体作用奠定基础。

During prostate gland organogenesis the fetal urogenital sinus mesenchyme induces and directs the phenotypic differentiation of the apposing epithelium. This leads to the formation of glandular ducts and acini, typical of the adult gland morphology. Previous studies from Dr. Rowley's laboratory have used organ cultures of fetal urogenital sinus to identify potential growth and differentiation regulatory factors from mesenchyme. These studies have identified a growth inhibitory factor in the conditioned medium from urogenital sinus organ cultures and derived mesenchymal cell lines. In addition, the growth inhibitory activity affects bladder and prostatic epithelial cell lines, suggesting this activity may affect cell differentiation. The protein responsible for activity has been purified to near homogeneity. The long term goals of this project are to understand the fundamental role of this factor, termed UGIF, in mesenchymal epithelial interactions during organogenesis. The immediate objectives of the studies proposed here are: to develop antibody and oligonucleotide probes specific for the UGIF protein; to isolate and clone the cDNA encoding UGIF and; to determine the spatial and temporal pattern of expression of UGIF in vivo. The proposed studies will set the foundation to determine the potential significance of UGIF as a regulatory factor in vivo, and its specific role in the basic mechanisms of mesenchymal epithelial interactions and associated organogenesis.