食管鳞状细胞癌中Survivin与Smac蛋白的表达及临床意义
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摘要
目的:研究Survivin和Smac蛋白在食管鳞状细胞癌组织及其对应正常组织中的表达情况,以及与临床生物学指标的关系。方法:运用Western blot检测Survivin和Smac在42例食管鳞癌患者标本中的表达量,分析蛋白表达与患者临床资料的关系。结果:Survivin在食管鳞癌中的表达较正常组织高(t=25.733,P<0.05),Smac在癌旁正常组织的表达高于食管癌组织(t=7.510,P<0.05),且都有显著性差异。二者在肿瘤组织中的含量与肿瘤分化程度及淋巴结转移有关(P<0.05)。Survivin和Smac蛋白在肿瘤组织中表达呈负相关(r=-0.407,P=0.008)。结论:Survivin和Smac蛋白在食管鳞癌组织中表达异常,提示两者参与了食管鳞癌的发生发展和肿瘤转移。
Objective:To investigate the expression of Survivin and Smac proteins in esophageal squamous cell carcinoma(ESCC) tissue and their relationship to the clinical and biological data.Methods:Expressions of Survivin and Smac proteins were detected by Western blot in 42 cases of ESCC.Results:The expression of Survivin in esophageal squamous cell carcinoma was significantly higher than in normal tissues(t=25.733,P<0.05),while the expression of Smac in the adjacent normal tissues was significantly higher than in esophageal carcinoma(t=7.510,P<0.05).Both of two genes had correlation with tumor differentiation and lymph node metastasis(P<0.05).In addition,Survivin had negative coralation with Smac in ESCC(r=-0.407,P=0.008).Conclusion:Abnormal expression of Survivin and Smac occured in ESCC suggests that Survivin and Smac play an important role in the development and metastasis of ESCC.
Objective:To investigate the expression of Survivin and Smac proteins in esophageal squamous cell carcinoma(ESCC) tissue and their relationship to the clinical and biological data.Methods:Expressions of Survivin and Smac proteins were detected by Western blot in 42 cases of ESCC.Results:The expression of Survivin in esophageal squamous cell carcinoma was significantly higher than in normal tissues(t=25.733,P<0.05),while the expression of Smac in the adjacent normal tissues was significantly higher than in esophageal carcinoma(t=7.510,P<0.05).Both of two genes had correlation with tumor differentiation and lymph node metastasis(P<0.05).In addition,Survivin had negative coralation with Smac in ESCC(r=-0.407,P=0.008).Conclusion:Abnormal expression of Survivin and Smac occured in ESCC suggests that Survivin and Smac play an important role in the development and metastasis of ESCC.
引文
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[3]Shi Y.Mechanisms of Caspase activation and inhibition during ap-optosis[J].Mol Cell,2002,9(3):459-470.
[4]Porter AG,Jnicke RU.Emerging roles of Caspase-3 in apoptosis[J].Cell Death Differ,1999,6(2):99-104.
[5]Bodmer JL,Holler N,Reynard S,et al.TRAIL receptor-2 signalsapoptosis through FADD and Caspase-8[J].Nat Cell Biol,2000,2(4):241-243.
[6]Tamm I,Wang Y,Sausville E,et al.IAP-family protein survivininhibits caspase activity and apoptosis induced by Fas(CD95),Bax,caspases,and anticancer drugs[J].Cancer Res,1998,58(23):5315-5320.
[7]Shin S,Sung BJ,Cho YS,et al.An anti-apoptotic protein humansurvivin is a direct inhibitor of caspase-3 and-7[J].Biochemis-try,2001,40(4):1117-1123.
[8]Bank A,Wang P,Du C,et al.SMAC mimetics sensitize nonsteroi-dal anti-inflammatory drug-induced apoptosis by promotingcaspase-3-mediated cytochrome c release[J].Cancer Res,2008,68(1):276-284.
[9]Kulathila R,Vash B,Sage D,et al.The structure of the BIR3 do-main of cIAP1 in complex with the N-terminal peptides of SMACand caspase-9[J].Acta Crystallogr D Biol Crystallogr,2009,65:58-66.
[10]Du C,Fang M,Li Y,et al.Smac,a mitochondrial protein that pro-motes cytochrome c-dependent caspase activation by eliminatingIAP inhibition[J].Cell,2000,102(1):33-42.
[11]Miyachi K,Sasaki K,Onodera S,et al.Correlation between sur-vivin mRNA expression and lymph node metastasis in gastriccancer[J].Gastric Cancer,2003,6(4):217-224.
[12]Ambrosini G,Adida C,Altieri DC.A novel anti-apoptosis gene,survivin,expressed in cancer and lymphoma[J].Nat Med,1997,3(8):917-921.
[13]Verdecia MA,Huang H-k,Dutil E,et al.Structure of the humananti-apoptotic protein survivin reveals a dimeric arrangement[J].Nat Struct Mol Biol,2000,7(7):602-608.
[14]Yagihashi A,Ohmura T,Asanuma K,et al.Detection of autoanti-bodies to survivin and livin in sera from patients with breast canc-er[J].Clinica Chimica Acta,2005,362(1-2):125-130.
[15]Altieri DC.Survivin,versatile modulation of cell division and ap-optosis in cancer[J].Oncogene,2003,22(53):8581-8589.
[16]Zhang XD,Zhang Y.Tumor necrosis factor related apoptosis-in-ducing ligand-induced apoptosis of human melanoma is regulatedby Smac/DIABLO release from mitochondria[J].Cancer Res,2001,61(19):7339-7348.
[17]McNeisha IA,Ell S,McKay T,et al.Expression of Smac/DIABLOin ovarian carcinoma cells induces apoptosis via a caspase-9-mediated pathway[J].Exp Cell Res,2003,286(2):186.
[18]Sekimura A,Konishki A.Expression of Smac/DIABLO is a novelprognostic marker in lung cancer[J].Oncol Rep,2004,11(4):797-802.
[19]Kempkensteffen C,Hinz S,Christoph F,et al.Expression levels ofthe mitochondrial IAP antagonists Smac/DIABLO and Omi/HtrA2in clear-cell renal cell carcinomas and their prognostic value[J].J Cancer Res Clin Oncol,2008,134(5):543-550.
[20]Bao ST,Gui SQ,Lin MS.Relationship between expression of Smacand Survivin and apoptosis of primary hepatocellular carcinoma[J].Hepatobiliary Pancreat Dis Int,2006,5(4):580-583.
[21]McNeisha IA,Lopesa R,Bell SJ,et al.Survivin interacts withSmac/DIABLO in ovarian carcinoma cells but is redundant inSmac-mediated apoptosis[J].Exp Cell Res,2005,302:69-82.