MARSHALL U COBRE: SKI AND SNO TRANSCRIPTION FACTORS IN TESTICULAR CANCERS

MARSHALL U COBRE：睾丸癌中的滑雪和滑雪转录因子

• 批准号: 7720786
• 负责人: LAURA L RICHARDSON
• 金额: $ 23.53万
• 依托单位: MARSHALL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720786
• 关键词: Address; Birds; Cell Lineage; Cell Proliferation; Cell physiology; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Disease; Event; Fibroblasts; Funding; Gene Expression; Genes; Germ Cells; Germ cell tumor; Grant; Human; Institution; Lead; Malignant neoplasm of testis; Marshal; Meiosis; Mitotic; Molecular; Mus; Nature; Pattern; Protein Overexpression; Proteins; Proto-Oncogenes; Regulation; Research; Research Personnel; Resources; SKI gene; SKIL gene; Signal Pathway; Skiing; Source; Spermatocytes; Spermatogonia; Testicular Neoplasms; Testicular malignant germ cell tumor; Testing; Transcription Coactivator; United States National Institutes of Health; Vitamin A; Withdrawal; base; data modeling; male; men; mouse model; protein expression; reproductive; restoration; transcription factor; tumorigenesis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Testicular cancer is a disease that afflicts young men in their peak reproductive years. Most testicular cancers are of germ cell origin and little is known about the molecular basis of tumorigenesis in germ cells. The proto-oncogenes Sk/and Sno were firs t identified as transforming agents in avian fibroblasts. They are widely expressed and paradoxically have been implicated in both transformation and differentiation. They act as both transcriptional activators and repressors. Preliminary data indicate t h at Ski and Sno are overexpressed in human testicular tumors. Ski and Sno gene expression also was detected in mouse germ cells with the highest levels observed in mitotic spermatogonia and early meiotic leptotene/zygotene spermatocytes, which span the t ra nsition between proliferation and differentiation in the germ cell lineage. Since this is the first demonstration of Ski and Sno in germ cells, their regulation and function has not been examined in germ cells These observations lead to the central h yp othesis of this proposal: that altered expression of the Ski and/or Sno genes in germ cell tumors changes the nature of transcriptional regulatory complexes containing these proteins, thereby interrupting the precisely controlled proliferation necessar y f or normal germ cell function. The objective of this proposal is to begin to understand the function of SKI and SNO in male germ cells through two specific aims. Aim One will determine how SKI and/or SNO are altered in testicular tumors by examining ge ne a nd protein expression patterns. SKI and SNO have been implicated in several different signaling pathways, but it is unknown how they act in germ cells. Therefore, Aim Two will address this question by focusing on the protein interactions of SKI an d S NO in th e vitamin A deficient mouse model, in which proliferation can be controlled by the withdrawal and restoration of vitamin A. Data from this model will be used as a basis for testing the function of SKI and SNO in germ cell tumors. The data ob t aine d fro m the proposed research will advance our understanding of the molecular events controlling germ cell proliferation in normal germ cells and promoting transformation in germ cell tumors.dtnnSK

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 睾丸癌是一种疾病，使年轻人在峰值生殖年中受苦。大多数睾丸癌是生殖细胞起源的，对生殖细胞中肿瘤发生的分子基础知之甚少。原始基因SK/和SNO被识别为鸟类成纤维细胞中的转化剂。它们被广泛表达，并且自相矛盾的是与转化和分化有关。它们既充当转录激活器和阻遏物。初步数据表明在滑雪和SNO处的T H过表达 在人类睾丸肿瘤中。在有丝分裂精子症和早期减数分裂瘦烯/Zygotene精子细胞中观察到的小鼠生殖细胞中还检测到了滑雪和SNO基因表达，这些细胞在生殖细胞谱系中的增殖与分化之间的T r r n s nsition。由于这是生殖细胞中滑雪和SNO的第一个证明，因此在生殖细胞中尚未对其调节和功能进行调查，这些观察结果导致该提案的中心含量：这种建议改变了生殖细胞肿瘤中SKI和/或SNO基因的表达，这会改变了含有这些蛋白质的转录调节性络合物的性质，从而导致了这些蛋白质，从而导致了这些蛋白质的泛滥泛滥。 正常生殖细胞功能。该提案的目的是通过两个特定目标开始了解男性生殖细胞中滑雪和SNO的功能。 AIM ONE将通过检查NE和GE NE和ND蛋白表达模式来确定如何在睾丸肿瘤中改变滑雪和/或SNO。滑雪和SNO已与几种不同的信号通路有关，但尚不清楚它们在生殖细胞中的作用。因此，目标两个将通过关注维生素A中的滑雪蛋白相互作用来解决这个问题 缺乏小鼠模型，其中可以通过戒断和恢复维生素A进行控制。该模型的数据将用作测试生殖细胞肿瘤中滑雪和SNO功能的基础。拟议的研究将提出我们对控制正常生殖细胞生殖细胞增殖并促进生殖细胞肿瘤转化的分子事件的理解。DTNNSK。