ROLE OF GLIL IN BASAL CELL CARCINOMA DEVELOPMENT

描述：(改编自调查人员的摘要) 本次拨款申请的项目是了解分子机制。 是基底细胞癌发生的潜在原因。具体地说，他们专注于 他们对Gli1在诱导基底细胞癌发生和发展中的潜在作用的研究 在对锌指调控机制的理解中 转录因子。 他们之前已经证明，Gli1而不是Gli3是始终如一的 在人类散发性基底细胞癌中表达，并足以诱导 在青蛙胚胎的皮肤中形成的表皮肿瘤。因为Gli1是一个 Sonic hedgehog(Shh)信号的靶标和介体Gli1转录 代表Shh信号通路的激活。这是一致的 以前的发现中，基因拼接，编码跨膜 Shh的受体对该途径有负面影响，在 家族性BCC。Patted基因的突变被认为是导致 基底细胞痣综合征。 他们建议使用青蛙来测试Gli2在BCC形成中的作用 胚胎检测及其在散发性疾病中的表达情况 人类的BCC。此外，他们还建议为BCC开发一种小鼠模型 在转基因小鼠中通过产生可诱导的Gli1蛋白而形成。 最后，他们建议建立Gli1功能的体内报告测试。 这些实验旨在为研究分子提供一个很好的模型。 BCC形成的基础，可能提供发展的机会 未来的抗癌药物。此外，了解如何 Shh信号通路和Gli1功能失调导致基底细胞癌 形成，将有助于揭示该基因在卵泡中的正常作用 发展。

DESCRIPTION: (adapted from the investigator's abstract) The goal of the project in this grant application is to understnad the molecular mechanisms underlying the development of basal cell cancer. Specifically, they focus their research in the potential role of Gli1 in inducing BCC development and in the understanding of the mechanisms regulated by this zinc finger transcription factor. They have previously shown that Gli1, but not Gli3, is consistently expressed in human sporadic BCCs and that it is sufficient to induce epidermal tumor formation in the skin of frog embryos. Because Gli1 is a target and mediator of Sonic hedgehog (Shh) signaling, Gli1 transcription represents the activation of the Shh signaling pathway. This is consistent with previous findings in which the gene Patched, encoding a transmembrane receptor for Shh having a negative effect on the pathway, is mutated in familial BCCs. Mutations in Patched are thought to be responsible for the Basal cell Nevus Syndrome. They propose to test for the role of Gli2 in BCC formation using the frog embryo assay and to test for the prevalence of its expression in sporadic human BCCs. In addition, they propose to develop a mouse model for BCC formation by the generation of an inducible Gli1 protein in transgenic mice. Finally, they propose to create an in vivo reporter assay for Gli1 function. The experiments are designed to provide a good model to study the molecular basis of BCC formation which may offer the opportunity to develop anti-cancer agents in the future. In addition, understanding how deregulation of the Shh signaling pathway and Gli1 function lead to BCC formation, will shed light into the normal role of this gene in follicle development.