ROLE OF GLIL IN BASAL CELL CARCINOMA DEVELOPMENT

GLIL 在基底细胞癌发展中的作用

• 批准号: 2896632
• 负责人: Ariel Ruiz i Altaba
• 金额: $ 26.77万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2896632
• 关键词: Xenopus oocyte; basal cell carcinoma; biological signal transduction; disease /disorder model; gene expression; genetically modified animals; human tissue; laboratory mouse; model design /development; molecular oncology; neoplastic process; transcription factor

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.

描述：（改编自研究者的摘要） 该赠款申请中的项目是了解分子机制 基底细胞癌发展的基础。 具体来说，他们关注 他们对 Gli1 在诱导 BCC 发展中的潜在作用的研究和 了解该锌指调节的机制 转录因子。 他们之前已经表明，Gli1（而非 Gli3）始终如一地发挥作用。 在人类散发的 BCC 中表达并且足以诱导 青蛙胚胎皮肤中表皮肿瘤的形成。 因为 Gli1 是 Sonic hidehog (Shh) 信号传导、Gli1 转录的靶标和介体 代表Shh信号通路的激活。 这是一致的 与之前的发现相比，该基因已修补，编码跨膜 Shh 受体对通路有负面影响，在 家族性 BCC。 Patched 中的突变被认为是导致 基底细胞痣综合症。 他们建议使用青蛙测试 Gli2 在 BCC 形成中的作用 胚胎测定并测试其在散发性胚胎中表达的普遍性 人类 BCC。 此外，他们建议开发 BCC 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，他们建议创建一种针对 Gli1 功能的体内报告基因检测方法。 这些实验旨在提供一个良好的模型来研究分子 BCC 形成的基础，可能提供发展机会 未来的抗癌药物。 此外，了解如何 Shh 信号通路和 Gli1 功能的失调导致 BCC 形成，将揭示该基因在卵泡中的正常作用 发展。