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Title: | 上皮生長因子接受器突變之小細胞肺癌細胞間異性授予存活優勢 Cellular heterogeneity confers survival benefit of small cell lung cancer harboring EGFR mutation |
Authors: | Chih-An Lin 林志安 |
Advisor: | 俞松良 |
Keyword: | 小細胞肺癌,肺腺癌,表皮生長因子接受器,抗藥性,組織蛋白去乙醯?, Small cell lung cancer,lung adenocarcinoma,Epidermal growth factor receptor (EGFR),TKI-resistance,histone deacetylase (HDAC), |
Publication Year : | 2017 |
Degree: | 博士 |
Abstract: | Transformation to small cell lung cancer (SCLC) is one of mechanisms for acquired resistance to Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) therapy in lung adenocarcinoma. Approximately 5% of patients with EGFR activating mutations acquire EGFR-TKIs resistance through SCLC transformation. However, the molecular basis of EGFR mutant SCLC transformed from adenocarcinoma was remains unclear. Therefore, we established two EGFR mutant SCLC cell lines from the patients who had EGFR activating mutations and received EGFR-TKIs. Interestingly, both cell lines have two different morphologies, suspended and attached types. Comparative genomic hybridization (CGH) analysis revealed that both type of each cell lines shared the same genomic alterations. Increased expression of EGFR and mesenchymal markers and decreased expression of neuroendocrine markers were observed in attached cells. Further, attached cells had lower colony forming ability but exhibited promoting colony forming ability to suspended type cells. Principal component analysis (PCA) and Hierarchical clustering analysis of genome wide RNA expression revealed that EGFR mutant SCLC cells display a unique gene expression pattern distinctly different from NSCLC and classical SCLC cells. Finally, the cell viability of EGFR mutant SCLC cells was strongly inhibited by histone deacetylase (HDAC) inhibitor FK-228(Ropmidepsin). This finding provides a clue for developing therapeutic strategy to overcome EGFR TKI resistance by SCLC transformation. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20423 |
DOI: | 10.6342/NTU201704005 |
Fulltext Rights: | 未授權 |
Appears in Collections: | 醫學檢驗暨生物技術學系 |
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ntu-106-1.pdf Restricted Access | 4.12 MB | Adobe PDF |
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