Downregulated expression of HSP27 in human low-grade glioma tissues discovered by a quantitative proteomic analysis.

Downregulated expression of HSP27 in human low-grade glioma tissues discovered by a quantitative proteomic analysis.
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定量蛋白质组学分析发现人低级别胶质瘤组织中 HSP27 表达下调

DOI:
10.1186/1477-5956-8-17
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发表时间:
2010-03-26
期刊:
影响因子:
2
通讯作者:
Wei Y
Wei Y
中科院分区:
生物学4区
文献类型:
--
作者:
Shen G;Liang S;Xu Z;Zhou L;Xiao S;Xia X;Li R;Liao Y;You C;Wei Y

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热休克蛋白(Heat shock proteins,HSP)是一类在进化过程中高度保守的蛋白质,主要包括HSP 110、HSP 90、HSP 70、HSP 60和小HSP家族。HSPs在多种肿瘤中的异常表达表明,特异性的HSPs对不同的肿瘤有不同的预后意义。在目前的研究中,在人类低级别胶质瘤组织(HGTs)的HSP的表达谱进行了研究,使用一个敏感的,准确的SILAC(稳定同位素标记与氨基酸在细胞培养)为基础的定量蛋白质组strategy.ResultsThe五个HSP家族成员的检测和定量HGTs和自体癌旁脑组织(PBTs)的SILAC为基础的质谱(MS)的同时。HGTs中HSP 90 AB 1、HSPA 5(70 KDa)表达明显下调,HSP 27表达明显下调,而HSPA 9(70 KDa)表达水平略高于PBTs。RT-PCR、Western blotting和免疫组化结果进一步证实了HGTs中HSP 27的下调率是PBTs的0.48倍。结论SILAC-MS技术是一种高通量、实用、高效的定量比较脑肿瘤中HSP 27相对表达水平的新方法。SILAC-MS分析发现不同HSP家族成员在人类低级别胶质瘤中具有特异性蛋白表达水平。热休克处理(43°C/0-3 h)后,HGTs中HSP 27的表达明显低于PBTs中HSP 27的表达,且HGTs中HSP 27的表达存在时空差异。HSP 27的快速上调可能与胶质瘤细胞对热休克的暂时抵抗有关,从而维持胶质瘤细胞的存活。
BackgroundHeat shock proteins (HSPs), including mainly HSP110, HSP90, HSP70, HSP60 and small HSP families, are evolutionary conserved proteins involved in various cellular processes. Abnormal expression of HSPs has been detected in several tumor types, which indicates that specific HSPs have different prognostic significance for different tumors. In the current studies, the expression profiling of HSPs in human low-grade glioma tissues (HGTs) were investigated using a sensitive, accurate SILAC (stable isotope labeling with amino acids in cell culture)-based quantitative proteomic strategy.ResultsThe five HSP family members were detected and quantified in both HGTs and autologous para-cancerous brain tissues (PBTs) by the SILAC-based mass spectrometry (MS) simultaneously. HSP90 AB1, HSP A5(70 KDa), and especially HSP27 were significantly downregulated in HGTs, whereas the expression level of HSPA9 (70 KDa) was little higher in HGTs than that in PBTs. It was noted that the downregulation ratio of HSP27 was 0.48-fold in HGTsversusPBTs, which was further validated by results from RT-PCR, western blotting and immunohistochemistry. Furthermore, we detected HSP27 expression changes along with cell growth under heat shock treatment in glioma H4 cells.ConclusionThe SILAC-MS technique is an applicable and efficient novel method, with a high-throughput manner, to quantitatively compare the relative expression level of HSPs in brain tumors. Different HSP family members have specific protein expression levels in human low-grade glioma discovered by SILAC-MS analysis. HSP27 expression was obviously downregulated in HGTsversusPBTs, and it exhibited temporal and spatial variation under heat shock treatment (43°C/0-3 h)in vitro. HSP27's rapid upregulation was probably correlated with the temporary resistance to heat shock in order to maintain the survival of human glioma cells.
DOI: 10.1074/jbc.271.28.16510
发表时间: 1996-07-12
影响因子: 4.8
作者:
Mehlen, P;SchulzeOsthoff, K;Arrigo, AP
通讯作者: Arrigo, AP
DOI: 10.1007/bf00666207
发表时间: 1994-01-01
影响因子: 3.8
作者:
FUQUA, SAW;OESTERREICH, S;OSBORNE, CK
通讯作者: OSBORNE, CK
DOI: 10.1002/prca.200800198
发表时间: 2009-06-01
影响因子: 2
作者:
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DOI: 10.1002/bjs.1800780321
发表时间: 1991-03-01
影响因子: 9.6
作者:
HARRISON, JD;JONES, JA;MORRIS, DL
通讯作者: MORRIS, DL
DOI: 10.1002/elps.200900249
发表时间: 2009-12-01
期刊: ELECTROPHORESIS
影响因子: 2.9
作者:
Liang, Shufang;Xu, Yuhuan;Wei, Yuquan
通讯作者: Wei, Yuquan