CREB-TARGET GENES IN MALIGNANT MESOTHELIOMA

恶性间皮瘤中的 CREB ​​靶基因

• 批准号: 7959898
• 负责人: ARTI SHUKLA
• 金额: $ 0.68万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959898
• 关键词: Asbestos; Cell Line; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; Cyclic AMP-Responsive DNA-Binding Protein; Data; Data Analyses; Development; Drug resistance; Funding; Gene Expression; Gene Targeting; Genes; Genetic; Grant; Greater sac of peritoneum; Growth; Human; Institution; Laboratories; Link; Malignant Neoplasms; Malignant mesothelioma; Mesothelial Cell; Mesothelioma; Microarray Analysis; Neoplasms; Patients; Pharmaceutical Preparations; Pleural; Process; Research; Research Personnel; Resistance Process; Resources; Role; Source; Surface; Tissue Microarray; United States National Institutes of Health; Vermont; angiogenesis; migration; programs; protein activation; 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. Malignant mesotheliomas (MMs) are aggressive neoplasms that are derived from the surface serosal cells of the pleural and peritoneal cavities. MM is associated with asbestos exposure however, little is known about the crucial cellular mechanisms contributing to the development and chemoresistance of MM. cAMP response element binding protein (CREB) is a transcription factor that rgulates a variety of cellular functions. CREB-dependent gene expression is also linked to various functions like growth/survival, migration/invasion, angiogenesis and drug resistance. The role of CREB has been studied in a few cancers but its role in MM is completely unknown. Data from our laboratory show increased activation of CREB and CREB-regulated genes in human mesothelial cells after asbestos exposure as well increased endogenous activation of CREB in 5 human MM lines and in tissue arrays from 3 MM patients. We hypothesized that CREB activation leads to expression of CREB-regulated genes involved in various tumorigenesis and drug resistance process of MM. In the present proposal we studied by microarray analysis (U133A2 Affymetrix chip and GeneSifter program to analyze data) common CREB-regulated genes after transfecting two different MM cell lines (Hmeso and PPMMill) with sh CREB or negative control. This study revealed a set of CREB-regulated genes involved in various tumorigenec processes in Hmeso (167 increased and 279 decreased more than 2 fold) and PPMMill (1555 increased and 2144 decreased more than 2 fold) mesothelioma cell lines. Functional relevance of identified genes in two MM cell lines will be validated and explored in a larger study. Identified genes could possibly act as potential target for MM treatment either alone or in combination with chemotherapeutic drugs.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 恶性间皮瘤（malignant mesotheliomas，简称MM）是一种侵袭性肿瘤，起源于胸膜腔和腹膜腔的表面浆膜细胞。MM与石棉接触有关，但对MM发生和耐药的关键细胞机制知之甚少。cAMP反应元件结合蛋白（CREB）是一种调节多种细胞功能的转录因子。CREB依赖性基因表达还与各种功能如生长/存活、迁移/侵袭、血管生成和耐药性相关。CREB的作用已经在一些癌症中进行了研究，但其在MM中的作用完全未知。我们实验室的数据显示，暴露于石棉后，CREB和CREB调节基因在人间皮细胞中的活化增加，以及CREB在5个人MM细胞系和3个MM患者的组织阵列中的内源性活化增加。我们假设CREB激活导致CREB调节基因的表达，这些基因参与MM的各种肿瘤发生和耐药过程。在本提议中，我们通过微阵列分析（U133 A2 Affyellow芯片和GeneSifter程序来分析数据）研究了两种不同的MM细胞系（Hmeso和PPMMill）与sh CREB或阴性对照一起转染后的共同CREB调节基因。这项研究揭示了一组CREB调节基因参与Hmeso（167增加和279减少超过2倍）和PPMMill（1555增加和2144减少超过2倍）间皮瘤细胞系中的各种致瘤过程。将在一项更大规模的研究中验证和探索两种MM细胞系中已鉴定基因的功能相关性。已识别的基因可能单独或与化疗药物联合作为MM治疗的潜在靶点。