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研究生： 蘇延霖
Su, Yen-Lin
論文名稱： 探討STK11抑制對於乳癌紫杉醇抗藥性的影響
The Effect of STK11 Suppression on Paclitaxel Resistance in Breast Cancer
指導教授： 徐慧萍
Hsu, Hui-Ping
學位類別： 碩士
Master
系所名稱： 醫學院 - 生物化學暨分子生物學研究所
Department of Biochemistry and Molecular Biology
論文出版年： 2024
畢業學年度： 112
語文別： 英文
論文頁數： 55
中文關鍵詞： 乳癌 、絲氨酸/蘇氨酸激酶11 、蛋白質合成 、細胞增生 、細胞凋亡 、紫杉醇抗藥性 、多重抗藥蛋白1 、ATP轉運蛋白E1
外文關鍵詞： breast cancer, STK11, protein synthesis, cell proliferation, apoptosis, paclitaxel resistance, MDR1, ABCE1
相關次數： 點閱：201  下載：0 
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    • 學位考試合格證明 i 摘要 ii Abstract iv Acknowledgments vi Table of contents vii Introduction 1 Breast cancer 1 Serine/Threonine kinase 11 (STK11) 4 Biological functions of STK11 4 STK11/AMPK/mTORC1 pathway and ribosomal protein S6 4 STK11/AMPK/mTORC1 pathway and apoptosis 5 STK11/AMPK/mTORC1 pathway and drug resistance 6 ATP-binding cassette E1 (ABCE1) 8 Rationale and hypothesis 10 Specific aims 11 Materials and methods 12 Cell culture 12 Breast tissue specimens 12 Plasmid DNA extraction 12 STK11-knockdown cell generation 13 Cell proliferation 13 Cell viability of paclitaxel treatment 14 Puromycin incorporation assay 14 RNA isolation, reverse transcription, and quantitative real-time PCR (qPCR) 15 Western blot 16 Statistical analysis 17 Results 18 Aim 1. To evaluate the expression of STK11 and its correlation with ABCE1 in breast cancer. 18 Aim 2. To evaluate protein synthesis, cell proliferation, and apoptosis in STK11-knockdown breast cancer cells. 19 Aim 3. To investigate the effect of STK11 suppression on sensitivity to paclitaxel. 21 Discussion 22 Conclusion 25 Figures 26 Figure 1. Gene expression of STK11, STRAD, and CAB39 in breast cancer from GEPIA2 database. 26 Figure 2. Correlation between STK11 and ABCE1 in breast cancer. 28 Figure 3. Transfection efficacy of each single clone. 29 Figure 4. The effect of STK11 suppression on AMPK/mTORC1/RPS6 signal transduction. 30 Figure 5. The effect of STK11 suppression on protein synthesis and cell proliferation. 31 Figure 6. The effect of STK11 suppression on apoptosis. 32 Figure 7. Paclitaxel sensitivity increased in STK11-knockdown MDA-MB-231 cells through decreasing the expression levels of MDR1. 34 Figure 8. Schematic summary of the effect of STK11 suppression on paclitaxel resistance, protein synthesis, cell proliferation, apoptosis, and ABCE1. 35 Tables 36 Table 1. pLKO.1-Puro cloning vectors and their target sequences. 36 Table 2. Demographics of 10 breast cancer patients. 37 References 40 Supplementary data 46

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