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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賴逸儒(I-Rue Lai) | |
| dc.contributor.author | Wan-Ting Hu | en |
| dc.contributor.author | 胡椀婷 | zh_TW |
| dc.date.accessioned | 2021-05-13T08:36:48Z | - |
| dc.date.available | 2018-08-26 | |
| dc.date.available | 2021-05-13T08:36:48Z | - |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-08 | |
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Cancer Gene Therapy, 21(11), 491-497. doi:10.1038/cgt.2014.55 29. Nieto, Y., Nawaz, F., Jones, R. B., Shpall, E. J., & Nawaz, S. (2007). Prognostic significance of overexpression and phosphorylation of epidermal growth factor receptor (EGFR) and the presence of truncated EGFRvIII in locoregionally advanced breast cancer. J Clin Oncol, 25(28), 4405-4413. doi:10.1200/JCO.2006.09.8822 30. Wang, F., Wang, S., Wang, Z., Duan, J., An, T., Zhao, J., & Bai, H. (2012). Phosphorylated EGFR expression may predict outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild type EGFR. J Exp Clin Cancer Res, 31, 65. 31. Magkou, C., Nakopoulou, L., Zoubouli, C., Karali, K., Theohari, I., Bakarakos, P., & Giannopoulou, I. (2008). Expression of the epidermal growth factor receptor (EGFR) and the phosphorylated EGFR in invasive breast carcinomas. Breast Cancer Res, 10(3), R49. doi:10.1186/bcr2103 32. Zhang, F., Tang, J. M., Wang, L., Shen, J. Y., Zheng, L., Wu, P. P., . . . Yan, Z. W. 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The prognostic impact of epidermal growth factor receptor in patients with metastatic gastric cancer. BMC Cancer, 12, 524. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/3789 | - |
| dc.description.abstract | 背景: 胃癌在癌症相關死亡率中高居第三位，雖然其發生率隨時間有逐漸下降的趨勢，但病人的預後仍然不佳，平均五年存活率只有29%。目前研究觀察到異常的醣化作用會影響癌細胞的惡性程度。在我們之前的研究發現乙烯半乳糖胺轉移酶2(Glycosyltransferase N-acetylgalactosaminyltransferase 2, GALNT2)在胃癌病人中表現量比正常胃腺組織少，其表現降低時會透過活化肝細胞生長因子受體(MET)而增加胃癌的惡性程度。此外，在受體酪氨酸激酶磷酸化陣列試驗(RTK array)中則觀察到降低GALNT2的表現量會增加表皮生長因子受體(Epidermal Growth Factor Receptor, EGFR)的活化，但對於GALNT2是否能透過調節EGFR的磷酸化而影響胃癌的進展依然是未知.
目的: 探討GALNT2是否能透過修飾EGFR醣基構造及調節磷酸化程度進而影響胃癌的惡性程度。 材料及方法: 以細胞株實驗分析，抑制GALNT2的表現後對於AGS的細胞存活率(MTT試驗)、轉移 (transwell migration assay) 及侵襲行為(matrigel invasion assay) 的影響。利用Vicia villosa agglutinin (VVA) pull down assay觀察EGFR的醣化作用。利用臨床胃癌檢體的免疫組織化學染色分析，pEGFR和GALNT2 表現與預後的相關性。 結果: 抑制GALNT2會增加EGFR和Akt磷酸化但減少EGFR的醣化作用。此外EGFR及Akt的抑制劑可以有效減少因抑制GALNT2而增加的轉移及侵襲能力，但細胞存活率在控制組及抑制GALNT2組別間不管是否有加入EGFR抑制劑都無顯著差異。臨床檢體中，44% (31/70)的病中人有表現pEGFR，且其與GALNT2表現量呈現正相關，但和其餘臨床病理特徵與預後沒有太大相關性。 結論: 在研究中觀察到GALNT2可以透過修飾EGFR醣化作用及減少其磷酸化和下游訊息傳遞而抑制胃癌細胞的惡性程度。 | zh_TW |
| dc.description.abstract | Background: Gastric cancer is the third leading cause of cancer-related deaths worldwide. Despite a steady decline in gastric cancer incidence and mortality, the overall 5-year survival rate of patients with gastric cancer is about 29%. Aberrant glycosylation affects the tumorigenesis and progression of cancers. In our previous study, we found that down-regulation of GALNT2 enhanced malignancy of gastric cancer as a result of increasing MET phosphorylation and affected activation of epidermal growth factor receptor (EGFR). Nevertheless, it remains unknown whether GALNT2 could regulate the malignancy through modifying EGFR phosphorylation.
Aims: To investigate whether GALNT2 could modify the malignant characteristics in gastric cancer by affecting EGFR phosphorylation and glycosylation. Materials and methods: Effects of GALNT2 knockdown on cell viability (MTT assay), migration (transwell migration assay) and invasion (matrigel invasion assay) of gastric cancer cell line (AGS) were analyzed. The Vicia villosa agglutinin (VVA) pull down assay was conducted to detect O-glycosylation of EGFR. Immunohistochemistry was performed to study the correlation of p-EGFR expression with GALNT2 and prognosis. Results: Knockdown of GALNT2 in AGS cells decreased the VVA binding to EGFR, but increased phosphorylation of EGFR and Akt. Furthermore, knockdown of GALNT2 enhanced the migration and invasion of AGS cells, which were reversed by treated with EGFR inhibitor (gefitinib) or Akt inhibitor (MK2206). However, there was no difference on cell viability between siC and siGALNT2-transfected groups, treated with either DMSO or gefitinib. Clinically, p-EGFR was over- expressed in 44% (31/70) of gastric cancer tissues. p-EGFR was positively correlated with GALNT2 but not associated with clinical outcomes. Conclusions: Our in vitro studies indicate that GALNT2 may suppress the malignancy of gastric cancer by modifying glycosylation of EGFR and reducing activation of EGFR-Akt pathway. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-13T08:36:48Z (GMT). No. of bitstreams: 1 ntu-105-R03446005-1.pdf: 46759103 bytes, checksum: 5e15754b516c764c3cab05c4feac74bd (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 審定書 i
致謝 ii 中文摘要 iii Abstract v I. Introduction 1 1-1. Gastric cancer 1 1-2. Mucin-type glycosylation 2 Introduction 2 Role of glycosylation in cancers 2 1-3. Epidermal growth factor receptor (EGFR) 4 EGFR and cancers 4 II. Aims 6 III. Materials and methods 7 3-1. Cell line 7 3-2. Western blot analysis 7 3-3. Immunohistochemistry 10 3-4. IHC evaluation 12 3-5. Real-time reverse transcription PCR (RT-PCR) 12 3-6. SiRNA knockdown of GALNT2 expression 14 3-7. MTT assay 14 3-8. Transwell migration assay 15 3-9. Matrigel invasion assay 16 3-10. VVA lectin pull down assay 16 3-11. Statistic analyses 16 IV. Results 18 4-1. Knockdown of GALNT2 increased epidermal growth factor receptor (EGFR) phosphorylation and decreased EGFR glycosylation. 18 4-2. Knockdown of GALNT2 enhanced the malignant phenotypes of gastric cancer through increasing EGFR phosphorylation in-vitro. 19 4-3. Knockdown of GALNT2 enhanced the malignant phenotypes of gastric cancer through increasing EGFR-Akt pathway in-vitro. 20 4.4 Correlation of p-EGFR with GALNT2 and clinico-pathological parameters. 21 V. Discussion 22 VI. Figures and table 27 Figure 1. Efficiency of GALNT2 knockdown. 27 Figure 2. Effect of GALNT2 knockdown on EGFR phosphorylation. 28 Figure 3. Effect of GALNT2 knockdown on EGFR glycosylation. 29 Figure 4. GALNT2 knockdown or gefitinib did not affect cell viability. 30 Figure 5. GALNT2 knockdown enhanced cell migration through increasing EGFR phosphorylation. 32 Figure 6. GALNT2 knockdown enhanced cell invasion through increasing EGFR phosphorylation. 34 Figure 7. Effect of EGFR inhibitor (gefitinib) on Akt and ERK1/2 phosphorylation and total form. 35 Figure 8. Inhibition of Akt phosphorylation decreased cell viability. 36 Figure 9. GALNT2 knockdown enhanced cell migration through increasing Akt phosphorylation. 38 Figure 10. GALNT2 knockdown enhanced cell invasion through increasing Akt phosphorylation. 40 Figure 11. Correlation between GALNT2 and p-EGFR expression. 41 Figure 12. Kaplan-Meier survival analysis of progression-free survival in gastric cancer patients with p-EGFR(+) or p-EGFR(-). 42 Table 1. Correlation between p-EGFR and clinico-pathological parameters. 43 VII. References 44 | |
| dc.language.iso | en | |
| dc.subject | 胃癌 | zh_TW |
| dc.subject | 乙烯半乳糖胺轉移? | zh_TW |
| dc.subject | 表皮生長因子受體 | zh_TW |
| dc.subject | O-醣基化 | zh_TW |
| dc.subject | Glycosyltransferase N-acetylgalactosaminyltransferase 2 (GALNT2) | en |
| dc.subject | gastric adenocarcinoma | en |
| dc.subject | O-glycosylation | en |
| dc.subject | Epidermal growth factor receptor (EGFR) | en |
| dc.title | 黏液蛋白醣化酵素GALNT2經由降低表皮生長因子接受器的磷酸化抑制胃癌的惡性程度 | zh_TW |
| dc.title | Mucin glycosylating enzyme GALNT2 suppresses the malignancy of gastric adenocarcinoma by reducing EGFR phosphorylation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃敏銓(Min-Chuan Huang),沈湯龍(Tang-Long Shen) | |
| dc.subject.keyword | 乙烯半乳糖胺轉移?,表皮生長因子受體,O-醣基化,胃癌, | zh_TW |
| dc.subject.keyword | Glycosyltransferase N-acetylgalactosaminyltransferase 2 (GALNT2),Epidermal growth factor receptor (EGFR),O-glycosylation,gastric adenocarcinoma, | en |
| dc.relation.page | 48 | |
| dc.identifier.doi | 10.6342/NTU201601951 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2016-08-08 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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