| Summary: | 碩士 === 臺灣大學 === 生醫電子與資訊學研究所 === 98 === Radiotherapy is commonly used for the treatment of many kinds of cancer such as retinoblastoma. However, an unexpected hypersensitivity to ionizing radiation in skin fibroblasts derived from unaffected parents of children with hereditary retinoblastoma was observed. The results from Dr. Chuang et al. used DNA microarray technology to select the 42 significantly differential expressed genes and identified as radiosensitive genes were observed in 2006. IGFBP5 (insulin-like growth factor binding protein 5), one of these 42 genes, was chosen to further investigate the role in radiosensitivity in fibroblast cells. In addition, IGFBP5 was reported that it was involved in the cellular senescence in endothelial cells. As the result, the topic of this thesis was to evaluate the role of IGFBP5 in radiosensitivity and cellular senescence in human fibroblast cells.
The results of this study showed IGFBP5 was involved in senescence by the method of SA-β-gal staining, cell proliferation assays, and the identification of genes related to anti-proliferation, cell-cycle arrest and senescence by the analysis of array data. Also, IGFBP5 played a role in radiosensitivity: Hs68 IGFBP5-overexpressed cells were more resistant to radiation at 2-4 Gy verified by colony formation assays. The radioresistace of IGFBP5 might be the lower proliferation rate of Hs68 IGFBP5-overexpressed cells and the up-regulation of PI3K-AKT pathway found from the analysis of array data.
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