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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50100完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李明學 | |
| dc.contributor.author | Yung-Hsun Kang | en |
| dc.contributor.author | 康詠洵 | zh_TW |
| dc.date.accessioned | 2021-06-15T12:29:43Z | - |
| dc.date.available | 2019-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-05 | |
| dc.identifier.citation | 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29.
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Mumenthaler SM, Ng PY, Hodge A, Bearss D, Berk G, Kanekal S, et al. Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther. 2009 Oct;8(10):2882-93. 121. van der Poel HG, Zevenhoven J, Bergman AM. Pim1 regulates androgen-dependent survival signaling in prostate cancer cells. Urol Int. 2010;84(2):212-20. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50100 | - |
| dc.description.abstract | 晚期攝護腺(前列腺)癌的患者預後往往極差,並且這類的癌細胞具有很強的侵襲、轉移能力。然而,這些癌細胞如何轉移的詳細機制目前仍然不是非常清楚。目前已知 PIM 激酶在晚期攝護腺癌中會大量表現,並且也有人將它視為預測攝護腺癌的指標之一。PIM1 激酶已知可以參與促進攝護腺癌生存、細胞增生以及細胞癌化的過程中,然而PIM1 如何、是否可以促使攝護腺癌細胞移動和轉移能力增加仍然需要更多的探討。在本篇研究中,我發現PIM1 表現量和攝護腺癌侵襲能力有正相關的關聯性,除此之外,抑制PIM1 表現量或利用他的抑制劑(SGI-1776)抑制其活性都可以有效抑制攝護腺癌細胞(DU145 & PC3)的移動能力。然而過度表達PIM1 可以顯著的提升人類胚胎腎臟細胞(HEK293T)以及攝護腺癌細胞(LNCaP)移動能力。此外,研究結果顯示鑲嵌於膜上的絲氨酸蛋白酶 Matriptase活性會受到PIM1 的影響。當抑制了Matriptase的表現量之下,也會抑制PIM1促使攝護腺癌細胞侵襲能力增加的這個現象。因此,綜合本篇的結果,暗示著PIM1 可以促使Matriptase 活化進而導致攝護腺癌細胞侵襲能力增加,並且可以作為未來治療攝護腺癌的藥物設計的重要目標。 | zh_TW |
| dc.description.abstract | Advanced prostate cancer (PCa) is poor prognosis with high metastasis. However, the molecular mechanism how advanced PCa acquires invasive and metastatic potential is still unclear. Several lines of evidences have shown that PIM kinase is up-regulated in advanced PCa and suggested as a prognostic biomarker for the cancer. In spite of the involvement of PIM1 in PCa cell survival, proliferation and tumorigenicity, whether PIM1 can also promote PCa cell motility and metastasis is still elusive. In this study, I found that the expression level of PIM1 was correlated with the capability of PCa cell invasion. Moreover, PIM1 silencing or treating with PIM1 inhibitor (SGI-1776) could inhibit PCa DU145 and PC3 cell invasion, while overexpression of PIM1 significantly increase the invasion capability of HEK293T and LNCaP cells. In addition, the results further showed that the activity of a membrane-anchored serine protease matriptase was affected by PIM1. Furthermore, matriptase silencing reduced PIM1-induced PCa cell invasion. Thus, the data together indicate that PIM1 can induce matriptase activation, leading to PCa cell invasion, and may serve as an important target for drug development for prostate cancer treatment. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T12:29:43Z (GMT). No. of bitstreams: 1 ntu-105-R03442005-1.pdf: 10841981 bytes, checksum: 74f4271bb32d6ce2ff513f73970c31f3 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 致謝 ......................................................................................................................... i
摘要 ....................................................................................................................... iii Abstract ................................................................................................................ iv Chapter 1. Introduction ........................................................................................... 1 Prostate cancer ...................................................................................................... 2 Cancer development and metastasis ..................................................................... 3 Proteolytic enzymes .............................................................................................. 4 1.1.1 Urokinase plasminogen activator (uPA)........................................................... 4 1.1.2 Matrix metalloproteinase (MMP) ..................................................................... 5 1.1.3 Matriptase ................................................................................................. 6-10 PIM1 (Proviral insertion site for Molony murine leukemia virus -1) -------------10-11 Research motivation ..............................................................................................12 Chapter 2. Material and Methods ..........................................................................13 2.1 Materials ..........................................................................................................14 2.1.1 Cell lines ........................................................................................................14 2.1.2 Antibodies .................................................................................................... 15 2.1.3 Enzymes ........................................................................................................15 2.1.4 Reagents ..................................................................................................16-18 2.1.5 Instruments ...................................................................................................18 2.2 Methods...........................................................................................................18 2.2.1 Cell culture ....................................................................................................18 2.2.2 Plasmid construction ..............................................................................19-20 2.2.3 Transfection ................................................................................................21 2.2.4 shRNA preparation and infection ...........................................................21-22 2.2.5 Cell cytotoxicity assay ...........................................................................22-23 2.2.6 Cell proliferation assay................................................................................ 23 2.2.7 Transwell invasion/migration assay .......................................................23-24 2.2.8 RNA extraction and quantitative real-time PCR (qRT-PCR) ....................24-27 2.2.9 Western blotting ....................................................................................27-28 2.2.10 Zymography assay ...............................................................................28-30 Chapter 3. Results ................................................................................................31 3.1 Correlation of PIM1 and prostate cancer cell motility ......................................32 3.2 Correlation of PIM1 and androgen dependency of prostate cancer ..........32-33 3.3 Role of PIM1 in prostate cancer cell motility....................................................34 3.4 Effect of PIM1 inhibitor (SGI-1776) on prostate cancer cell invasion..........34-35 3.5 Effect of PIM1 overexpression and its kinase activity on cell invasion........35-36 3.6 Role of PIM1 knockdown in metastasis-related proteases..........................36-37 3.7 Role of PIM1 overexpression in metastasis-related proteases....................38-39 3.8 PIM1 promote prostate cancer cell invasion through matriptase......................40 3.9 Matriptase acted as an effector for PIM1-induced prostate cancer cell invasion ........................................................................................................................40-41 3.10 Summary ......................................................................................................41 Chapter 4. Discussion....................................................................................42-47 Chapter 5. Figures......................................................................................... 48-74 Chapter 6. References ...................................................................................76-86 | |
| dc.language.iso | en | |
| dc.subject | PIM1 | zh_TW |
| dc.subject | 前列腺癌 | zh_TW |
| dc.subject | 侵襲能力 | zh_TW |
| dc.subject | 轉移 | zh_TW |
| dc.subject | Matriptase | zh_TW |
| dc.subject | 前列腺癌 | zh_TW |
| dc.subject | PIM1 | zh_TW |
| dc.subject | 侵襲能力 | zh_TW |
| dc.subject | 轉移 | zh_TW |
| dc.subject | Matriptase | zh_TW |
| dc.subject | Prostate cancer | en |
| dc.subject | Matriptase | en |
| dc.subject | Invasion | en |
| dc.subject | PIM1 | en |
| dc.subject | Prostate cancer | en |
| dc.subject | Matriptase | en |
| dc.subject | Invasion | en |
| dc.subject | PIM1 | en |
| dc.title | PIM1 在前列腺癌移動能力中扮演的角色 | zh_TW |
| dc.title | Role of PIM1 in prostate cancer cell motility | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 華國泰,顧記華,曾秀如 | |
| dc.subject.keyword | 前列腺癌,PIM1,侵襲能力,轉移,Matriptase, | zh_TW |
| dc.subject.keyword | Prostate cancer,PIM1,Invasion,Matriptase, | en |
| dc.relation.page | 86 | |
| dc.identifier.doi | 10.6342/NTU201602004 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-05 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位: | 生物化學暨分子生物學科研究所 | |
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