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Title: | SP110b在抑制癌症及基因調控上的角色 The roles of SP110b in tumor suppression and gene regulation |
Authors: | Chia-Wei Lin 林佳煒 |
Advisor: | 顏伯勳 |
Keyword: | SP110b,腫瘤抑制,CCL5,NF-κB,單核球移行, SP110b,tumor suppression,CCL5,NF-κB,monocyte migration, |
Publication Year : | 2015 |
Degree: | 碩士 |
Abstract: | 前骨髓性細胞白血病細胞核體 (Promyelocytic leukemia nuclear body; 簡稱PML-NB) 是位於細胞核中的特殊構造,其中會聚集許多種類的蛋白,並參與基因轉錄、細胞凋亡、腫瘤抑制及對抗病毒的相關機制。SP110 核蛋白為 PML-NB 的其中一個成員,而 SP110b 則為 SP110 蛋白的一個主要異構體。本論文研究發現 SP110b 的過量表現會顯著地抑制 H1299 肺癌細胞的生長和群落生成,在臨床分析也指出 SP110b 的高度表現會與肺癌病人的存活率呈正相關。另一方面,我們也觀察到當細胞遭受氧化壓力時,SP110b 的表現會促使細胞停留於細胞週期的 G0/G1 期,並在調控細胞週期的進程上扮演重要角色。在 SP110b 所參與的基因調控上,我們發現趨化因子 CCL5 的基因轉錄會被轉錄因子 NF-κB 所活化,而 SP110b 會相對地抑制這樣的活化作用。除此之外,在 SP110b 過量表現下,γ干擾素刺激所導致的單核球移行 (monocyte migration) 也會被明顯地抑制下來。總結以上的結果,本研究發現核蛋白 SP110b 具有許多不同的細胞功能,例如調控趨化因子的基因表現,進而影響單核球或其他免疫細胞在γ干擾素刺激下的移行能力。另外,SP110b 也是一個有潛力的肺癌腫瘤抑制因子,並且可能與良好的預後相關。 Promyelocytic leukemia nuclear body (PML-NB) is a discrete nuclear compartment that consists of various proteins involving in regulation of gene transcription, apoptosis, tumor suppression and antiviral response. SP110 nuclear protein is a PML-NB component, and SP110b is a major isoform of SP110. Here we demonstrated that SP110b significantly suppressed the growth and colony formation of H1299 cells and, in clinical, its expression is positively associated with a better survival of lung cancer patients. In addition, we also found that SP110b was critical for the alteration of cell cycle progression in response to oxidative stress via accumulation of cells in G0/G1 phase. In terms of the roles of SP110b in gene regulation, we demonstrated that nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-induced transcription of C-C motif ligand 5 (CCL5) chemokine was remarkably down-regulated by SP110b. Moreover, the extent of monocyte migration that is activated by interferon gamma (IFN-γ) treatment was impaired in the presence of SP110b over-expression. In sum, our findings suggest that SP110b nuclear protein has multiple cellular functions, such as regulating gene transcription of chemokines, thereby affecting migration of immune cells upon IFN-γ stimulation. Besides, SP110b also serves as a potential tumor suppressor of lung cancer that correlated with good prognosis. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19827 |
Fulltext Rights: | 未授權 |
Appears in Collections: | 生物化學暨分子生物學科研究所 |
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ntu-104-1.pdf Restricted Access | 2.28 MB | Adobe PDF |
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