ROLE OF GLIL IN BASAL CELL CARCINOMA DEVELOPMENT

描述：（改编自研究者摘要） 本基金申请的项目是了解 基底细胞癌的潜在发展。 具体来说，他们专注于 他们对Gli1在诱导BCC发展中的潜在作用的研究， 对锌指调控机制的理解 转录因子 他们之前已经证明，Gli1，而不是Gli3， 在人类散发性BCC中表达，并且足以诱导 青蛙胚胎皮肤中的表皮肿瘤形成。 因为Gli1是一个 Sonic hedgehog（Shh）信号转导靶点和介导因子，Gli1转录 代表Shh信号通路的激活。 这是一致 与先前的发现，其中基因补丁，编码跨膜 Shh的受体对该途径具有负面影响， 家族性BCC Patched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。 胚胎试验，并测试其在散发性 人类基底细胞癌 此外，他们建议开发一种BCC的小鼠模型， 通过在转基因小鼠中产生可诱导的Gli1蛋白来形成。 最后，他们建议建立一种用于Gli1功能的体内报告试验。 这些实验的目的是提供一个很好的模型来研究分子 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BCC 形成，将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.