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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 黃敏銓 | |
| dc.contributor.author | Chih-Hsing Chou | en |
| dc.contributor.author | 周志行 | zh_TW |
| dc.date.accessioned | 2021-06-16T03:47:38Z | - |
| dc.date.available | 2015-03-12 | |
| dc.date.copyright | 2015-03-12 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-01-28 | |
| dc.identifier.citation | Chapter 5. References
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Wang ZQ, Bachvarova M, Morin C, Plante M, Gregoire J, Renaud MC, Sebastianelli A and Bachvarov D. Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation. Oncotarget. 2014; 5(2):544-560. 45. Lillehoj EP, Han F and Kim KC. Mutagenesis of a Gly-Ser cleavage site in MUC1 inhibits ectodomain shedding. Biochemical and biophysical research communications. 2003; 307(3):743-749. 46. Julian J, Dharmaraj N and Carson DD. MUC1 is a substrate for gamma-secretase. Journal of cellular biochemistry. 2009; 108(4):802-815. 47. Boskovski MT, Yuan S, Pedersen NB, Goth CK, Makova S, Clausen H, Brueckner M and Khokha MK. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. Nature. 2013; 504(7480):456-459. 48. Kufe DW. Mucins in cancer: function, prognosis and therapy. Nature reviews Cancer. 2009; 9(12):874-885. 49. Alam M, Ahmad R, Rajabi H, Kharbanda A and Kufe D. MUC1-C oncoprotein activates ERK-->C/EBPbeta signaling and induction of aldehyde dehydrogenase 1A1 in breast cancer cells. The Journal of biological chemistry. 2013; 288(43):30892-30903. 50. Blixt O, Bueti D, Burford B, Allen D, Julien S, Hollingsworth M, Gammerman A, Fentiman I, Taylor-Papadimitriou J and Burchell JM. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis. Breast cancer research : BCR. 2011; 13(2):R25. 51. Burford B, Gentry-Maharaj A, Graham R, Allen D, Pedersen JW, Nudelman AS, Blixt O, Fourkala EO, Bueti D, Dawnay A, Ford J, Desai R, David L, Trinder P, Acres B, Schwientek T, et al. Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer. British journal of cancer. 2013; 108(10):2045-2055. 52. Astronomo RD and Burton DR. Carbohydrate vaccines: developing sweet solutions to sticky situations? 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55111 | - |
| dc.description.abstract | 根據世界衛生組織公佈乳癌佔全球女性癌症發生率與死亡率皆排名第一位。異常的醣化修飾常見於許多癌症發展過程中。Core 1 β1,3-galactosyltransferase (C1GALT1)為為黏液型醣化作用過程中唯一可以形成Core 1 structure (Gal-GalNAc-Ser/The)的醣化酵素，並且在許多腫瘤形成的過程中被發現C1GALT1有大量表現。從許多公開的RNA Microarray資料庫中我們發現C1GALT1 mRNA在乳癌腫瘤中表現增加，並且顯示高表現C1GALT1的病人其10年存活率相較低表現的病人差。此外，我們利用乳癌Tissue Microarray觀察C1GALT1蛋白質表現量也顯示C1GALT1在乳癌腫瘤組織中有大量表現，並且其表現量與病人的病理因子Grade與Stage成正相關。從in vitro與in vivo實驗證實C1GALT1可以促進乳癌細胞的惡性行為之特性，例如：細胞遷移、侵襲、癌幹細胞特性以及生長；同樣地抑制C1GALT1表現則會降低其惡性行為。此外，C1GALT1可以調控MUC1-N上的醣化結構，並且透過影響其下游MUC1-C/β-catenin/ERK訊號路徑，來調控乳癌細胞生長。本篇研究指出C1GALT1在乳癌腫瘤形成過程中扮演重要角色，未來在真對乳癌治療研究上提供一個具潛力的方向。 | zh_TW |
| dc.description.abstract | Core 1 β1,3-galactosyltransferase (C1GALT1) is an exclusive enzyme in humans that catalyzes the biosynthesis of core 1 O-glycan structure, Gal-GalNAc-O-Ser/Thr, whose expression is commonly up-regulated during tumorigenesis. Aberrant glycosylation is frequently observed in cancers. Breast cancer is the most frequently diagnosed malignancy in women and the first leading cause of cancer-related death worldwide. However, little is known about the function of C1GALT1 in breast cancer. Breast cancer is the most frequently diagnosed malignancy in women and the first leading cause of cancer-related death worldwide. This study aims to establish the correlation between C1GALT1 expression and breast cancer clinicopathological features and the roles of C1GALT1 in breast cancer malignant phenotypes. Public databases and our data show that C1GALT1 mRNA and protein are frequently up-regulated in breast cancer; and increased C1GALT1 expression correlates with higher histological grade and advanced tumor stage. Overexpression of C1GALT1 enhanced breast cancer cell growth, migration, and invasion in vitro and tumor growth in vivo. Conversely, C1GALT1 knockdown suppressed these malignant phenotypes. Furthermore, C1GALT1 modulated O-glycan structures on Mucin (MUC) 1 and promoted MUC1-C/β-catenin signaling in breast cancer cells. These findings suggest that C1GALT1 enhances breast cancer malignant progression by promoting MUC1-C/β-catenin signaling pathway. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T03:47:38Z (GMT). No. of bitstreams: 1 ntu-104-D00446004-1.pdf: 3260453 bytes, checksum: a28ae8f1b383366daa5ee198abb0c971 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | Table of Content
口試委員會審定書…………………………………………………………………....... i 致謝…………………………………………………………………………………...... ii 中文摘要…………………………………………………………...…………………. iii Abstract…………………………………………..…………………………………… iv Chapter 1. Introduction………..…………………………………………………………1 Chapter 2. Material and methods…….………..…………………………………………7 2.1 Immunohistochemistry………………………………………………………7 2.2 Cell lines and cell culture…………………………………………………...7 2.3 Transfection…………......…………………………………………………….8 2.4 T synthase activity assay………………………………………………….......9 2.5 Transwell migration and invasion assay……………………………...……..10 2.6 Sphere formation assay………………………………………………………10 2.7 Trypan blue exclusion assay..………………………………………………..10 2.8 MTT assay…………………………………………………………………...11 2.9 In vivo xenograft tumor growth model………………………………….…...11 2.10 Flow cytometry………………………………………………………………12 2.11 Western blot analysis and lectin pull-down assay.…...………….…………..12 2.12 Immunofluorescence microscopy…………………………………………..13 2.13 Quantitative (Q) RT-PCR analysis……………………………….……...…..14 2.14 Cell fractionation……….....…………………..……………………………..14 2.15 Statistical analysis…………………………………………………………15 Chapter 3. Results………...………….…………………………………………………16 3.1 C1GALT1 mRNA and protein are up-regulated in breast cancer………………………………………………………………………..16 3.2 High C1GALT1 expression correlates with breast cancer higher histological grade and advanced tumor stage….....………………………………………...16 3.3 C1GALT1 regulates O-glycan structures on surfaces of breast cancer cells....17 3.4 C1GALT1 regulates malignant behaviors of breast cancer cells......................18 3.5 C1GALT1 regulates breast cancer tumor growth in vivo……………………20 3.6 C1GALT1 regulates O-glycosylation of proteins in breast cancer cells…….21 3.7 C1GALT1 regulates O-glycan structures on MUC1……………………….…22 3.8 C1GALT1 regulates MUC1-N shedding into condition medium and MUC1-C translocation into the nucleus……………………………………………….23 3.9 C1GALT1 regulates MUC1-C/β-catenin signalling pathway………………...24 3.10 C1GALT1 promotes cell growth through MUC1-C pathway……………….25 Chapter 4. Discussion………………………………………………………………..…27 Chapter 5. References………….…………………………………….…………………32 Figures and Table Figure 1. C1GALT1 mRNA is frequently up-regulated in ductal carcinoma and basal-like breast cancer………………………………….....………………..38 Figure 2. C1GALT1 mRNA expression is correlated with breast cancer poor survival..……………………………………………………………………..39 Figure 3. C1GALT1 is frequently overexpressed in breast tumor tissues and correlates with histological grade and stage ………………………...…………………40 Figure 4. C1GALT1 is differentially expressed in multiple breast cancer cell lines……………………………………………………………..………….41 Figure 5. C1GALT1 regulates O-glycan structures on surfaces of breast cancer cells…..……………………………………………………………………...42 Figure 6. T synthase activity assay in breast cancer cells……………............………...43 Figure 7. C1GALT1 modulates breast cancer cell migration and invasion….................………………………………………………………..44 Figure 8. C1GALT1 modulates cancer stemness properties in breast cancer cells……………………………………….…………………………………45 Figure 9. C1GALT1 modulates breast cancer cell growth…………….………………46 Figure 10. Knockdown of C1GALT1 confirms suppression of T47D cell growth in vitro…………………………………………………………………………47 Figure 11. C1GALT1 promotes breast tumor growth in vivo………………………...48 Figure 12.C1GALT1 enhances breast cancer cell proliferation and O-glycans changes in xenograft tumors………………………………………………………….49 Figure 13.C1GALT1 regulates O-glycosylation of proteins in breast cancer cells….…50 Figure 14.Knockdown of C1GALT1 modifies O-glycans on MUC1-N in MDA-MB-231 and SKBR3 breast cancer cells………………………..……51 Figure 15.C1GALT1 regulates MUC1-N shedding in breast cancer cells…………….52 Figure 16.C1GALT1 regulates MUC1-C/β-catein/ERK signaling pathway in breast cancer cells…………………………………………………………………..53 Figure 17.C1GALT1 promotes cell growth through MUC1-C pathway………………54 Table Table 1. C1GALT1 expression level correlates with clinicopathological characteristics……….……………………………………………………….55 | |
| dc.language.iso | en | |
| dc.subject | 乳癌 | zh_TW |
| dc.subject | 黏液型醣化蛋白? | zh_TW |
| dc.subject | Breast cancer | en |
| dc.subject | C1GALT1 | en |
| dc.subject | MUC1 | en |
| dc.title | "Core 1 β1,3 galactosyltransferase (C1GALT1 )影響乳癌細胞惡性行為之研究" | zh_TW |
| dc.title | The role of Core 1 β1,3 galactosyltransferase (C1GALT1) in breast cancer cell malignant behaviors | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 李明學,賴逸儒,劉雅雯,陳啟豪 | |
| dc.subject.keyword | 乳癌,黏液型醣化蛋白?, | zh_TW |
| dc.subject.keyword | Breast cancer,C1GALT1,MUC1, | en |
| dc.relation.page | 55 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-01-29 | |
| 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 |
| Appears in Collections: | 解剖學暨細胞生物學科所 | |
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