MOLECULAR STUDIES OF RADIATION RESISTANT TUMOR CELLS

抗辐射肿瘤细胞的分子研究

• 批准号: 6443857
• 负责人: ANATOLY DRITSCHILO
• 金额: $ 34.88万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-02 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443857
• 关键词: DNA binding protein; antisense nucleic acid; basosquamous cell carcinoma; biological signal transduction; cell line; cellular oncology; cytogenetics; flow cytometry; gel mobility shift assay; gene expression; genetic regulation; human tissue; inhibitor /antagonist; ionizing radiation; molecular oncology; neoplasm /cancer genetics; neoplasm /cancer radiation therapy; northern blottings; nuclear factor kappa beta; polymerase chain reaction; radiation resistance; radiation sensitivity; reporter genes; southern blotting; transfection; western blottings

Signal transduction pathways play important roles in cellular responses to ionizing radiation. We have recently observed that one of these pathways, that involving the transcriptional factor NF-khib/ikhib, is implicated in t extreme radiation sensitivity of cells from patients with the human genetic disease, ataxia telangiectasia (AT). Furthermore, prelimary experiments wit human squamous carcinoma cells (SCCs) reveal that components of the NF- khib/-Ikhib complex are expressed at various levels, and show evidence of differences in message size. Since these cell lines have been previously characterized to show various intrinsic radiation sensitivities, we propose to investigate NF-NF-khib/NF-khib function in these radiation sensitive and radiation resistant human tumor cells (SCCs). We will test the hypothesis that impaired NF-khib regulation results in a more radiation sensitive cellular phenotype. Using a model cell system of three radiation sensitive and three radiation resistant SCCs, we will measure expression levels and structural integritie of genes coding for components of the NF-khibeta/1khibeta complex. DNA- protein binding assays, and reporter gene expression assays will determine the functional integrity of components of the complex. Chemical and biological inhibition experiments will determine whether radiation resistan cells can be made more sensitive in their response to ionizing radiation by interfering with the NF-khibeta signaling pathways. The completion of the experiments in this proposal will provide insight int the NF-khibeta pathway and its relationship to cellular radiation response. Such knowledge may identify useful molecular information for application in diagnostic and therapeutic strategies to improve the cancer treatment therapeutic ratio.

信号转导通路在细胞应答中起重要作用