Identification of tongue cancer related protein using proteomic and tissue array profiling

使用蛋白质组学和组织阵列分析鉴定舌癌相关蛋白

基本信息

批准号：
16591892
负责人：
TANUMA Jun-ichi
金额：
$ 2.18万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591892/
关键词：
Tongue carcinogenesis QTL analysis Candidate genes cDNA Microarray Protein array

项目摘要

Our group has previously used cDNA microarrays to characterize global transcriptional changes. These genes can be broadly categorized based upon their functions in metabolism, angiogenesis, invasion/tissue remodeling, apoptosis, and proliferation/differentiation. Many of these genes contribute to tumor progression and increased malignancy. However, transcriptional changes alone are not sufficient to characterize the complexity of the tumor cell response to hypoxia. Other investigators have reported a poor correlation between mRNA and protein abundance. Furthermore, a single gene can encode for more than one mRNA species through differential splicing, and proteins can undergo as many as 200 posttranslational modifications. These processes all contribute to a large number of different proteins that can be produced from a single gene. Interpretation of genomic and proteomic data are additionally complicated by the fact that we are only able to obtain a static picture of a highly complex, interrelated, and dynamic process.Currently, there are many competing technologies and approaches to identify carcinogenesis markers reliably for prognostic and therapeutic purposes. The aim of this study was to characterize global changes in the proteome. Using this approach, we have identified a group of hypoxia-regulated proteins that are induced by posttranscriptional mechanisms. These hypoxia-inducible proteins represent novel diagnostic/therapeutic targets. We also investigated the significance of one of these proteins, NQO1 and Pthrp, by correlating tumor carcinogenesis and metastatis with expression of this protein in squamous cell carcinomas of the tongue.

我们的小组以前已经使用cDNA微阵列来表征全局转录变化。这些基因可以基于它们在新陈代谢，血管生成，侵袭/组织重塑，凋亡和增殖/分化的功能中进行广泛分类。这些基因中的许多有助于肿瘤进展和恶性肿瘤。但是，单独的转录变化不足以表征肿瘤细胞对缺氧的复杂性。其他研究人员报告说，mRNA和蛋白质丰度之间的相关性较差。此外，单个基因可以通过差异剪接编码多个mRNA物种，蛋白质可以进行多达200个翻译后修饰。这些过程都有助于从单个基因产生的大量不同蛋白质。基因组和蛋白质组学数据的解释也使我们只能获得高度复杂，相互关联和动态过程的静态图片而变得复杂。目前，有许多竞争性的技术和方法可以可靠地识别预后和治疗用途的致癌作用。这项研究的目的是表征蛋白质组的全球变化。使用这种方法，我们已经确定了一组由转录后机制诱导的缺氧调节的蛋白质。这些缺氧诱导的蛋白质代表新的诊断/治疗靶标。我们还通过将肿瘤的癌变和递Mentastatis与该蛋白在舌头的鳞状细胞癌中的表达相关联，研究了这些蛋白质NQO1和PTHRP之一的重要性。