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人皮肤鳞状细胞癌中TCTP表达上调通过该蛋白的抗凋亡作用增加肿瘤细胞活力。

Upregulation of TCTP expression in human skin squamous cell carcinoma increases tumor cell viability through anti-apoptotic action of the protein.

作者信息

Wu DI, Guo Ze, Min Wei, Zhou Bingrong, Li Mingna, Li Wei, Luo Dan

机构信息

Departments of Dermatology, and.

出版信息

Exp Ther Med. 2012 Mar;3(3):437-442. doi: 10.3892/etm.2011.439. Epub 2011 Dec 28.

DOI:10.3892/etm.2011.439
PMID:22969908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3438791/
Abstract

The translationally controlled tumor protein (TCTP) is an anti-apoptotic protein, which is highly expressed in several human cancer types. However, the role of TCTP in skin cancers, including squamous cell carcinoma (SCC), has not been investigated. In this study, we analyzed the expression of TCTP in cutaneous SCC samples using immunohistochemistry in two epidermoid SCC cell lines, A431 and SCL-1, using western blot analysis. We further investigated the role of TCTP in skin cancinogenesis by silencing the TPT1 gene using small interfering RNA (siRNA) in the SCC cell line A431. Our results demonstrated that TCTP was overexpressed in cutaneous SCC cells, compared to normal skin keratinocytes. In addition, the expression of TCTP in skin SCC significantly increased with the grade of malignancy. Western blot analysis further confirmed that the expression of TCTP in the cell lines, A431 and SCL-1, was significantly higher compared to that in the normal keratinocyte cell line, HaCaT. The expression of TCTP in A431 cells was significantly downregulated by transfection with our specifically designed TCTP siRNA. We found that downregulation of TCTP expression was associated with decreased cell proliferation and increased apoptosis in A431 cells. These results suggest that the TPT1 gene may be a potential therapeutic target in skin SCC through a siRNA approach.

摘要

翻译调控肿瘤蛋白(TCTP)是一种抗凋亡蛋白,在多种人类癌症类型中高表达。然而,TCTP在包括鳞状细胞癌(SCC)在内的皮肤癌中的作用尚未得到研究。在本研究中,我们使用免疫组织化学分析了皮肤SCC样本中TCTP的表达,并在两种表皮样SCC细胞系A431和SCL-1中使用蛋白质印迹分析。我们通过在SCC细胞系A431中使用小干扰RNA(siRNA)沉默TPT1基因,进一步研究了TCTP在皮肤癌发生中的作用。我们的结果表明,与正常皮肤角质形成细胞相比,TCTP在皮肤SCC细胞中过表达。此外,TCTP在皮肤SCC中的表达随着恶性程度的增加而显著增加。蛋白质印迹分析进一步证实,与正常角质形成细胞系HaCaT相比,细胞系A431和SCL-1中TCTP的表达显著更高。通过转染我们专门设计的TCTP siRNA,A431细胞中TCTP的表达显著下调。我们发现TCTP表达的下调与A431细胞中细胞增殖的减少和凋亡的增加有关。这些结果表明,通过siRNA方法,TPT1基因可能是皮肤SCC的一个潜在治疗靶点。

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本文引用的文献

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Anti-apoptotic protein TCTP controls the stability of the tumor suppressor p53.抗凋亡蛋白 TCTP 控制肿瘤抑制因子 p53 的稳定性。
FEBS Lett. 2011 Jan 3;585(1):29-35. doi: 10.1016/j.febslet.2010.11.014. Epub 2010 Nov 17.
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The molecular programme of tumour reversion: the steps beyond malignant transformation.肿瘤逆转的分子程序:恶性转化之外的步骤。
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TCTP protects from apoptotic cell death by antagonizing bax function.TCTP通过拮抗bax功能来保护细胞免于凋亡性死亡。
Cell Death Differ. 2008 Aug;15(8):1211-20. doi: 10.1038/cdd.2008.18. Epub 2008 Feb 15.
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Fortilin binds Ca2+ and blocks Ca2+-dependent apoptosis in vivo.福替林结合钙离子并在体内阻断钙离子依赖性细胞凋亡。
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A knockout mouse approach reveals that TCTP functions as an essential factor for cell proliferation and survival in a tissue- or cell type-specific manner.基因敲除小鼠实验方法表明,TCTP以组织或细胞类型特异性的方式,作为细胞增殖和存活的关键因子发挥作用。
Mol Biol Cell. 2007 Jul;18(7):2525-32. doi: 10.1091/mbc.e07-02-0188. Epub 2007 May 2.
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An N-terminal region of translationally controlled tumor protein is required for its antiapoptotic activity.翻译后调控肿瘤蛋白的N端区域对于其抗凋亡活性是必需的。
Oncogene. 2005 Jul 14;24(30):4778-88. doi: 10.1038/sj.onc.1208666.
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Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP.TCTP对mcl-1抗凋亡活性的稳定与增强作用
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Translationally controlled tumor protein interacts with the third cytoplasmic domain of Na,K-ATPase alpha subunit and inhibits the pump activity in HeLa cells.翻译调控肿瘤蛋白与钠钾ATP酶α亚基的第三个胞质结构域相互作用,并抑制HeLa细胞中的泵活性。
J Biol Chem. 2004 Nov 26;279(48):49868-75. doi: 10.1074/jbc.M400895200. Epub 2004 Sep 21.
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TSAP6 facilitates the secretion of translationally controlled tumor protein/histamine-releasing factor via a nonclassical pathway.TSAP6通过非经典途径促进翻译调控肿瘤蛋白/组胺释放因子的分泌。
J Biol Chem. 2004 Oct 29;279(44):46104-12. doi: 10.1074/jbc.M404850200. Epub 2004 Aug 19.
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Identification of the interaction between the human recombinant histamine releasing factor/translationally controlled tumor protein and elongation factor-1 delta (also known as eElongation factor-1B beta).人重组组胺释放因子/翻译控制肿瘤蛋白与延伸因子-1δ(也称为延伸因子-1Bβ)之间相互作用的鉴定
Biochim Biophys Acta. 2004 Apr 5;1688(3):232-6. doi: 10.1016/j.bbadis.2003.12.007.