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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 林能裕(Neng-Yu Lin) | |
dc.contributor.author | Jia-Hsuan Lin | en |
dc.contributor.author | 林佳宣 | zh_TW |
dc.date.accessioned | 2021-06-17T04:58:19Z | - |
dc.date.available | 2018-08-01 | |
dc.date.copyright | 2018-08-01 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-07-26 | |
dc.identifier.citation | 1. Battafarano G, Rossi M, Marampon F, & Del Fattore A (2018) Cellular and Molecular Mediators of Bone Metastatic Lesions. Int J Mol Sci 19(6).
2. Body JJ, et al. (2017) Systematic review and meta-analysis on the proportion of patients with breast cancer who develop bone metastases. Crit Rev Oncol Hematol 115:67-80. 3. Brook N, Brook E, Dharmarajan A, Dass CR, & Chan A (2018) Breast cancer bone metastases: pathogenesis and therapeutic targets. Int J Biochem Cell Biol 96:63-78. 4. Buenrostro D, et al. (2018) Early TGF-beta inhibition in mice reduces the incidence of breast cancer induced bone disease in a myeloid dependent manner. Bone 113:77-88. 5. Cai WL, et al. (2018) microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11. Mol Cancer 17(1):9. 6. Chen YC, Sosnoski DM, & Mastro AM (2010) Breast cancer metastasis to the bone: mechanisms of bone loss. Breast Cancer Res 12(6):215. 7. Choi B, et al. (2014) Elevated Pentraxin 3 in bone metastatic breast cancer is correlated with osteolytic function. Oncotarget 5(2):481-492. 8. Cosphiadi I, et al. (2018) Bone Metastasis in Advanced Breast Cancer: Analysis of Gene Expression Microarray. Clin Breast Cancer. 9. Cox TR, et al. (2015) The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature 522(7554):106-110. 10. D'Oronzo S, Brown J, & Coleman R (2017) The value of biomarkers in bone metastasis. Eur J Cancer Care (Engl) 26(6). 11. Duong LT, Wesolowski GA, Leung P, Oballa R, & Pickarski M (2014) Efficacy of a cathepsin K inhibitor in a preclinical model for prevention and treatment of breast cancer bone metastasis. Mol Cancer Ther 13(12):2898-2909. 12. Fang J & Xu Q (2015) Differences of osteoblastic bone metastases and osteolytic bone metastases in clinical features and molecular characteristics. Clin Transl Oncol 17(3):173-179. 13. Fu C, et al. (2016) Tumor-associated antigens: Tn antigen, sTn antigen, and T antigen. HLA 88(6):275-286. 14. Giehl K, Imamichi Y, & Menke A (2007) Smad4-independent TGF-beta signaling in tumor cell migration. Cells Tissues Organs 185(1-3):123-130. 15. Gill DJ, et al. (2013) Initiation of GalNAc-type O-glycosylation in the endoplasmic reticulum promotes cancer cell invasiveness. Proc Natl Acad Sci U S A 110(34):E3152-3161. 16. Gold LI (1999) The role for transforming growth factor-beta (TGF-beta) in human cancer. Crit Rev Oncog 10(4):303-360. 17. Gregory LS, Choi W, Burke L, & Clements JA (2013) Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice. PLoS One 8(9):e68103. 18. Guise TA & Chirgwin JM (2003) Transforming growth factor-beta in osteolytic breast cancer bone metastases. Clin Orthop Relat Res (415 Suppl):S32-38. 19. Haider MT & Taipaleenmaki H (2018) Targeting the Metastatic Bone Microenvironment by MicroRNAs. Front Endocrinol (Lausanne) 9:202. 20. He Z, et al. (2014) MAPK11 in breast cancer cells enhances osteoclastogenesis and bone resorption. Biochimie 106:24-32. 21. Heldin P, Basu K, Kozlova I, & Porsch H (2014) HAS2 and CD44 in breast tumorigenesis. Adv Cancer Res 123:211-229. 22. Ho CW, et al. (2016) The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn. Oncotarget 7(38):61930-61944. 23. Hsieh CJ, et al. (2015) Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling. Int J Oncol 46(2):555-562. 24. Imamura T, Hikita A, & Inoue Y (2012) The roles of TGF-beta signaling in carcinogenesis and breast cancer metastasis. Breast Cancer 19(2):118-124. 25. Irshad I & Varamini P (2018) Different Targeting Strategies For Treating Breast Cancer Bone Metastases. Curr Pharm Des. 26. Javelaud D, et al. (2011) TGF-beta/SMAD/GLI2 signaling axis in cancer progression and metastasis. Cancer Res 71(17):5606-5610. 27. Johnston SR, Dowsett M, & Smith IE (1992) Towards a molecular basis for tamoxifen resistance in breast cancer. Ann Oncol 3(7):503-511. 28. Ju T, Aryal RP, Kudelka MR, Wang Y, & Cummings RD (2014) The Cosmc connection to the Tn antigen in cancer. Cancer Biomark 14(1):63-81. 29. Jun AY, et al. (2014) Tetrahydrofurofuran-type lignans inhibit breast cancer-mediated bone destruction by blocking the vicious cycle between cancer cells, osteoblasts and osteoclasts. Invest New Drugs 32(1):1-13. 30. Kaklamani V & Pasche B (2005) Transforming Growth Factor Beta and breast cancer. Cancer Treat Res 126:129-156. 31. Kamalakar A, et al. (2014) Circulating interleukin-8 levels explain breast cancer osteolysis in mice and humans. Bone 61:176-185. 32. Kolbl AC, Jeschke U, Friese K, & Andergassen U (2016) The role of TF- and Tn-antigens in breast cancer metastasis. Histol Histopathol 31(6):613-621. 33. Koli KM & Arteaga CL (1996) Complex role of tumor cell transforming growth factor (TGF)-beta s on breast carcinoma progression. J Mammary Gland Biol Neoplasia 1(4):373-380. 34. Kozlow W & Guise TA (2005) Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia 10(2):169-180. 35. Krawetz R, Wu YE, Rancourt DE, & Matyas J (2009) Osteoblasts suppress high bone turnover caused by osteolytic breast cancer in-vitro. Exp Cell Res 315(14):2333-2342. 36. Lee SK, et al. (2015) Platycodin D Blocks Breast Cancer-Induced Bone Destruction by Inhibiting Osteoclastogenesis and the Growth of Breast Cancer Cells. Cell Physiol Biochem 36(5):1809-1820. 37. Liu S, et al. (2018) Osteocyte-Driven Downregulation of Snail Restrains Effects of Drd2 Inhibitors on Mammary Tumor Cells. Cancer Res. 38. Luftner D, Niepel D, & Steger GG (2018) Therapeutic approaches for protecting bone health in patients with breast cancer. Breast 37:28-35. 39. Lynch ME, et al. (2013) In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model. J Bone Miner Res 28(11):2357-2367. 40. Ma Y, Liu H, Zhang H, & Shao RG (2015) [The TGF-beta signaling pathway induced EMT in breast cancer]. Yao Xue Xue Bao 50(4):385-392. 41. Marino S, et al. (2018) Regulation of breast cancer induced bone disease by cancer-specific IKKbeta. Oncotarget 9(22):16134-16148. 42. McCoy EM, Hong H, Pruitt HC, & Feng X (2013) IL-11 produced by breast cancer cells augments osteoclastogenesis by sustaining the pool of osteoclast progenitor cells. BMC Cancer 13:16. 43. Milde-Langosch K, et al. (2015) Relevance of betaGal-betaGalNAc-containing glycans and the enzymes involved in their synthesis for invasion and survival in breast cancer patients. Breast Cancer Res Treat 151(3):515-528. 44. Monteiro AC, et al. (2013) T cells induce pre-metastatic osteolytic disease and help bone metastases establishment in a mouse model of metastatic breast cancer. PLoS One 8(7):e68171. 45. Moore-Smith L & Pasche B (2011) TGFBR1 signaling and breast cancer. J Mammary Gland Biol Neoplasia 16(2):89-95. 46. Neophytou C, Boutsikos P, & Papageorgis P (2018) Molecular Mechanisms and Emerging Therapeutic Targets of Triple-Negative Breast Cancer Metastasis. Front Oncol 8:31. 47. Nickerson NK, et al. (2012) Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad. PLoS One 7(1):e30255. 48. Norgaard P, Damstrup L, Spang-Thomsen M, & Poulsen HS (1992) [Transforming growth factor beta. A potent multifunctional growth factor for normal and malignant cells]. Ugeskr Laeger 154(49):3494-3498. 49. Norgaard P, Hougaard S, Poulsen HS, & Spang-Thomsen M (1995) Transforming growth factor beta and cancer. Cancer Treat Rev 21(4):367-403. 50. O'Conor CJ, Chen T, Gonzalez I, Cao D, & Peng Y (2018) Cancer stem cells in triple-negative breast cancer: a potential target and prognostic marker. Biomark Med. 51. Ouyang Z, et al. (2018) Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway. Oncotarget 9(2):1868-1884. 52. Owen S, et al. (2017) Key Factors in Breast Cancer Dissemination and Establishment at the Bone: Past, Present and Future Perspectives. Adv Exp Med Biol 1026:197-216. 53. Park BK, et al. (2007) NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF. Nat Med 13(1):62-69. 54. Parkes A, et al. (2018) Characterization of bone only metastasis patients with respect to tumor subtypes. NPJ Breast Cancer 4:2. 55. Peramuhendige P, et al. (2018) TRAF2 in osteotropic breast cancer cells enhances skeletal tumour growth and promotes osteolysis. Sci Rep 8(1):39. 56. Porter K & Rosenzweig MQ (2017) Current and Emerging Therapies for HER2-Positive Women With Metastatic Breast Cancer. J Adv Pract Oncol 8(2):164-168. 57. Pulido C, et al. (2017) Bone metastasis risk factors in breast cancer. Ecancermedicalscience 11:715. 58. Rao S, Cronin SJF, Sigl V, & Penninger JM (2018) RANKL and RANK: From Mammalian Physiology to Cancer Treatment. Trends Cell Biol 28(3):213-223. 59. Reiss M & Barcellos-Hoff MH (1997) Transforming growth factor-beta in breast cancer: a working hypothesis. Breast Cancer Res Treat 45(1):81-95. 60. Rose AA & Siegel PM (2006) Breast cancer-derived factors facilitate osteolytic bone metastasis. Bull Cancer 93(9):931-943. 61. Schrijver W, et al. (2018) Receptor Conversion in Distant Breast Cancer Metastases: A Systematic Review and Meta-analysis. J Natl Cancer Inst 110(6):568-580. 62. Sisay M, Mengistu G, & Edessa D (2017) The RANK/RANKL/OPG system in tumorigenesis and metastasis of cancer stem cell: potential targets for anticancer therapy. Onco Targets Ther 10:3801-3810. 63. Smith HS, Stern R, Liu E, & Benz C (1991) Early and late events in the development of human breast cancer. Basic Life Sci 57:329-337; discussion 337-340. 64. Song K, et al. (2015) Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice. J Biol Chem 290(33):20159-20166. 65. Sung B, Oyajobi B, & Aggarwal BB (2012) Plumbagin inhibits osteoclastogenesis and reduces human breast cancer-induced osteolytic bone metastasis in mice through suppression of RANKL signaling. Mol Cancer Ther 11(2):350-359. 66. Tulotta C & Ottewell P (2018) The role of IL-1B in breast cancer bone metastasis. Endocr Relat Cancer 25(7):R421-R434. 67. Vishal M, Swetha R, Thejaswini G, Arumugam B, & Selvamurugan N (2017) Role of Runx2 in breast cancer-mediated bone metastasis. Int J Biol Macromol 99:608-614. 68. Wright LE, et al. (2013) Curcuminoids block TGF-beta signaling in human breast cancer cells and limit osteolysis in a murine model of breast cancer bone metastasis. J Nat Prod 76(3):316-321. 69. Wu MY, et al. (2018) Molecular Regulation of Bone Metastasis Pathogenesis. Cell Physiol Biochem 46(4):1423-1438. 70. Yoneda T, Sasaki A, & Mundy GR (1994) Osteolytic bone metastasis in breast cancer. Breast Cancer Res Treat 32(1):73-84. 71. Zheng H, Li W, & Kang Y (2016) Tumor-Stroma Interactions in Bone Metastasis: Molecular Mechanisms and Therapeutic Implications. Cold Spring Harb Symp Quant Biol 81:151-161. 72. Zheng X, Kang W, Liu H, & Guo S (2018) Inhibition effects of total flavonoids from Sculellaria barbata D. Don on human breast carcinoma bone metastasis via downregulating PTHrP pathway. Int J Mol Med 41(6):3137-3146. 73. Zu X, et al. (2012) Transforming growth factor-beta signaling in tumor initiation, progression and therapy in breast cancer: an update. Cell Tissue Res 347(1):73-84. 74. Band AM & Laiho M (2011) Crosstalk of TGF-beta and estrogen receptor signaling in breast cancer. J Mammary Gland Biol Neoplasia 16(2):109-115. 75. Barcellos-Hoff MH & Akhurst RJ (2009) Transforming growth factor-beta in breast cancer: too much, too late. Breast Cancer Res 11(1):202. 76. Barcellos-Hoff MH & Ewan KB (2000) Transforming growth factor-beta and breast cancer: Mammary gland development. Breast Cancer Res 2(2):92-99. 77. Buijs JT, et al. (2007) TGF-beta and BMP7 interactions in tumour progression and bone metastasis. Clin Exp Metastasis 24(8):609-617. 78. Chang CF, Westbrook R, Ma J, & Cao D (2007) Transforming growth factor-beta signaling in breast cancer. Front Biosci 12:4393-4401. 79. Chargari C, Toillon RA, Macdermed D, Castadot P, & Magne N (2009) Concurrent hormone and radiation therapy in patients with breast cancer: what is the rationale? Lancet Oncol 10(1):53-60. 80. Chow A, Arteaga CL, & Wang SE (2011) When tumor suppressor TGFbeta meets the HER2 (ERBB2) oncogene. J Mammary Gland Biol Neoplasia 16(2):81-88. 81. Cicek M & Oursler MJ (2006) Breast cancer bone metastasis and current small therapeutics. Cancer Metastasis Rev 25(4):635-644. 82. Dickson RB & Lippman ME (1988) Control of human breast cancer by estrogen, growth factors, and oncogenes. Cancer Treat Res 40:119-165. 83. Drabsch Y & ten Dijke P (2011) TGF-beta signaling in breast cancer cell invasion and bone metastasis. J Mammary Gland Biol Neoplasia 16(2):97-108. 84. Fazilaty H, Gardaneh M, Bahrami T, Salmaninejad A, & Behnam B (2013) Crosstalk between breast cancer stem cells and metastatic niche: emerging molecular metastasis pathway? Tumour Biol 34(4):2019-2030. 85. Tan AR, Alexe G, & Reiss M (2009) Transforming growth factor-beta signaling: emerging stem cell target in metastatic breast cancer? Breast Cancer Res Treat 115(3):453-495. 86. Taylor MA, Lee YH, & Schiemann WP (2011) Role of TGF-beta and the tumor microenvironment during mammary tumorigenesis. Gene Expr 15(3):117-132. 87. Walker RA (2000) Transforming growth factor beta and its receptors: their role in breast cancer. Histopathology 36(2):178-180. 88. Wang J & Wu J (2012) Role of miR-155 in breast cancer. Front Biosci (Landmark Ed) 17:2350-2355. 89. Wang W, Nag SA, & Zhang R (2015) Targeting the NFkappaB signaling pathways for breast cancer prevention and therapy. Curr Med Chem 22(2):264-289. 90. Yamaguchi M, Vikulina T, & Weitzmann MN (2015) Gentian violet inhibits MDA-MB-231 human breast cancer cell proliferation, and reverses the stimulation of osteoclastogenesis and suppression of osteoblast activity induced by cancer cells. Oncol Rep 34(4):2156-2162. 91. Yip CH & Rhodes A (2014) Estrogen and progesterone receptors in breast cancer. Future Oncol 10(14):2293-2301. 92. Zabkiewicz C, Resaul J, Hargest R, Jiang WG, & Ye L (2017) Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance. Endocr Relat Cancer 24(10):R349-R366. 93. Zafonte BT, et al. (2000) Cell-cycle dysregulation in breast cancer: breast cancer therapies targeting the cell cycle. Front Biosci 5:D938-961. 94. Zarzynska JM (2014) Two faces of TGF-beta1 in breast cancer. Mediators Inflamm 2014:141747. 95. Zhang L, et al. (2013) TRAF4 promotes TGF-beta receptor signaling and drives breast cancer metastasis. Mol Cell 51(5):559-572. 96. Zhang Y, Ma B, & Fan Q (2010) Mechanisms of breast cancer bone metastasis. Cancer Lett 292(1):1-7. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71201 | - |
dc.description.abstract | 乳癌為女性最常見的惡性腫瘤,而有近七成的乳癌會發生骨轉移。一旦發生骨轉移,病人會產生劇烈疼痛、病理性骨折、神經壓迫與運動功能障礙,因此乳癌骨轉移一直是一個棘手的問題。近年研究指出,溶骨性的乳癌骨轉移中,巨噬細胞集落刺激因子(macrophage colony-stimulating factor ; M-CSF)及核因子κ-B配體受體致活劑(Receptor activator of nuclear factor kappa-B ligand ; RANKL)可促進蝕骨細胞的分化,進而加速骨質溶解。黏蛋白種類O-醣基化為最常見的蛋白質轉譯後修飾之一,在合成O-glycan結構的過程中,Galβ1,3GalNAc稱為T antigen 或Core 1 structure,在正常組織中可被醣化轉換酵素延伸成更長的結構。 core 1 β1,3-galactosyltransferase (C1GALT1)為黏蛋白種類O-醣基化作用中可形成Core 1 structure (Gal-GalNAc-ser/The)的醣類轉移酶,而C1GALT1的分子伴侶chaperone Cosmc為C1GALT1活化所必須的。過去研究指出,C1GALT1會在乳癌細胞中大量表現,並且可以調控乳癌細胞的惡性行為。因此我們想知道,醣類轉移酶C1GALT1與其分子伴侶Cosmc在乳癌所誘導的蝕骨細胞生成中所扮演的角色。當乳癌發生骨轉移時,TGF-β(transforming growth factor-β)會因蝕骨作用而從bone matrix中釋出,然而大量的TGF-β也會促使乳癌細胞生長,形成一個惡性循環。因此我們想探討TGF-β與C1GALT1在乳癌骨轉移中是否有調控的機制。
在我們的研究中發現,C1GALT1會受TGF-β細胞激素調控。當MDA-MB-231下調C1GALT1與Cosmc後,其細胞表面的Tn抗原有累積的現象。為了更進一步了解C1GALT1與蝕骨細胞分化的關係,我們將小鼠骨髓細胞與乳癌細胞的培養基共培養。從TRAP staining與Bone Resorption assay的結果顯示,C1GALT1下調(knockdown)後,可抑制蝕骨細胞的分化。另外,由即時聚合酶連鎖反應及西方點墨法的實驗結果也可發現,下調C1GALT1與Cosmc後,RANKL及M-CSF的表現量皆下降。另外,在動物模式中,我們對小鼠進行乳癌細胞心臟注射,並將小鼠的骨頭以Micro CT分析,發現C1GALT1 Knockdown的組別其骨破壞的程度較低。因此綜合上述實驗結果,我們認為在乳癌細胞中下調C1GALT1可以抑制由乳癌細胞所誘導的蝕骨細胞分化,希望未來可以找到治療的標的,進而減緩乳癌骨轉移的發生。 | zh_TW |
dc.description.abstract | Breast cancer is the most diagnosed malignancy among women worldwide, and bones are a common place for breast cancer cells to metastasize. More recently, several studies have concluded the potential mechanisms of osteolytic bone metastasis in breast cancer is referred to high level of cancer cell secreted Macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL), activators important for osteoclast differentiation. Mucin-type O-glycosylation is one of the most common post-translational modifications of proteins and it is associated with many important biological functions. Aberrant glycosylation of cell surface is associated with malignant transformation of breast cancer. Core 1 ß1,3 galactosyltransferase (C1GALT1) controls the biosynthesis of core 1 O-glycan structure, which is called T antigen. Cosmc is a molecular chaperone thought to be required for expression of active T-synthase, the only enzyme that galactosylates the Tn-antigen to form T antigen. In previous study, overexpression of C1GALT1 has recently been shown to be related to the malignant phenotypes of breast cancer cells. In the bone matrix, transforming growth factor-β (TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteolytic bone resorption. TGF-β stimulates bone metastatic tumor cells to secrete factors that further drive osteolytic bone destruction adjacent to the tumor. Thus, TGF-β is a crucial factor responsible for driving the feed-forward vicious cycle of cell growth in bone. This study aims to determine the correlation between T-antigen and breast cancer bone metastasis. Our data show that knockdown C1GALT1 and Cosmc in MDA-MB-231 suppressed the mRNA and protein level of RANKL and M-CSF. Downexpression of C1GALT1 in breast cancer cell prevented osteoclast differentiation in vitro and increased the bone density by intra-cardic injection of breast cancer cells. These findings suggests that exposure of Tn-antigen in breast cancer cell suppress bone metastasis and prevented osteoclast differentiation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T04:58:19Z (GMT). No. of bitstreams: 1 ntu-107-R05446009-1.pdf: 2368453 bytes, checksum: 82264ff819f51cbe2723a9c71ba0d0f0 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 誌謝--i
中文摘要--ii Abstract--iii 目錄(Contents)--iv 第一章、緒論(Introduction--1 1.1 乳癌--2 1.1.1 背景--2 1.1.2 乳癌的分類--2 1.1.3 乳癌的分期與治療--3 1.1.4 乳癌骨轉移--3 1.1.5 骨轉移的種類--5 1.1.6 溶骨性(osteolytic)骨轉移、蝕骨細胞生成 (osteoclastogenesis)與乳癌的關係--5 1.2 乙型轉化生長因子(Transforming Growth Factor ; TGF-β--6 1.2.1 TGF-β 在骨骼平衡中所扮演的角色--6 1.2.2 TGF-β 與癌症的關係--7 1.2.3 TGF-β 與乳癌骨轉移的關係--8 1.3 醣基化(Glycosylation )--8 1.3.1 黏蛋白O 聚醣--8 1.3.2 異常黏蛋白型O 聚醣與乳癌--9 第二章、材料與研究方法 (Materials and Methods) --10 2.1 實驗材料(Materials) --11 2.1.1 抗體(Antibody)--11 2.1.2 引子(Primers) --11 2.1.3 其他(others) --12 2.2 實驗方法(Methods) --14 2.2.1 細胞株與細胞培養(cell line and cell culture) --14 2.2.2 病毒載體感染乳癌細胞株MDA-MB-231--14 2.2.3 RNA 萃取以及即時聚合酶連鎖反應(RNA Extraction & RT-PCR)--14 2.2.4 流式細胞儀(Flow cytometry)--15 2.2.5 蛋白質定量(Bradford protein assay)--15 2.2.6 西方點墨法(Western Blot analysis) --16 2.2.7 組織石蠟包埋與切片(Paraffin embedding & paraffin section) --17 2.2.8 骨組織脫鈣--18 2.2.9 蘇木精-依紅染色(H&E Stain) --18 2.2.10 破骨細胞活性酵素抗酒石酸酸性磷酸酶染色--19 2.2.11 骨組織之破骨細胞活性酵素抗酒石酸酸性磷酸酶染色--19 2.2.12 骨再吸收定量(Bone resorption assay) --20 2.2.13 小鼠骨髓細胞與乳癌細胞培養液共培養--20 2.2.14 凝集素VVA-FITC 染色--21 2.2.15 螢光素酶檢測法(Luciferase Assay systems)--21 2.2.16 細胞記數--21 2.2.17 乳癌骨轉移動物模式:心臟注射(Intra-Cardic Injection)--22 2.2.18 乳癌細胞小鼠脛骨內注射(Intra-tibial Injection)--22 2.2.19 統計分析(Statistical analyses)--22 第三章、結果(Results)--23 3.1 在乳癌細胞株MDA-MB-231 中,TGF-β 可以調控C1GALT1 之表現--24 3.2 在乳癌細胞株MDA-MB-231 中,下調C1GALT1、Cosmc 會改變乳癌細胞表面的醣類結構,並增加Tn-antigen 的累積--24 3.3 C1GALT1 knockdown 能抑制蝕骨細胞分化--25 3.4 C1GALT1 knockdown 能減緩骨吸收作用--26 3.5 C1GALT1 與Cosmc 能調控RANKL 與M-CSF 的表現量--26 3.6 小鼠心臟注射(Intra-Cardiac injection)中,下調C1GALT1 能減緩骨吸收作用--27 3.7 小鼠脛骨內注射(Intra-Tibial injection)中,C1GALT1 knockdown 的乳癌細胞能減緩骨頭破壞--28 第四章、結論(Conclusion) --30 第五章、討論(Discussion) --32 5.1.1 醣基轉移酶與癌症--33 5.1.2 過度呈現C1GALT1 是否會促進蝕骨細胞分化?--34 5.1.3 醣基轉移酶是否會影響PTHrP 的分泌? --34 5.1.4 TGF-β 與C1GALT1 在乳癌細胞中的調控關係--35 5.1.5 PU.1 在蝕骨細胞生成中所扮演的角色--35 第六章、圖表(Figures) --37 第七章、參考文獻(References) --51 | |
dc.language.iso | zh-TW | |
dc.title | 藉由調控乳癌細胞 MDA-MB-231 之C1GALT1 可抑制其所導致之蝕骨細胞生成 | zh_TW |
dc.title | C1GALT1 knockdown in MDA-MB-231cells suppresses breast cancer cell-induced osteoclatogenesis. | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃敏銓(Ming-Chuan Huang),蔡明霖(Ming-Lin Tsai),李建智(Jian-Jr Lee) | |
dc.subject.keyword | 乳癌,醣類轉換酵素,蝕骨細胞,黏蛋白型 O-聚醣, | zh_TW |
dc.subject.keyword | Breast cancer,C1GALT1,Mucin-type O-glycosylation,osteoclastogenesis, | en |
dc.relation.page | 55 | |
dc.identifier.doi | 10.6342/NTU201801943 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-07-27 | |
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 |
文件中的檔案:
檔案 | 大小 | 格式 | |
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ntu-107-1.pdf 目前未授權公開取用 | 2.31 MB | Adobe PDF |
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