食管鳞癌中MEKK3和NF-κB的表达及其临床意义
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摘要
目的研究有丝分裂原活化蛋白激酶激酶激酶3(MEKK3)、核转录因子(NF-κB)蛋白在食管鳞癌组织中的表达及其临床意义。方法收集76例食管鳞癌患者的癌组织及相应的35例癌旁异型增生组织和20例正常食管黏膜组织,应用免疫组化EnVision法检测MEKK3、NF-κB蛋白的表达。结果食管鳞癌组织中MEKK3蛋白阳性表达率高于癌旁异型增生组织和正常食管黏膜组织(均P<0.05);NF-κB蛋白表达阳性率在正常食管黏膜组、癌旁异型增生组、食管鳞癌组中依次升高;MEKK3、NF-κB蛋白表达与临床分期、浸润深度及淋巴结转移均相关(均P<0.05),而与患者年龄、性别及组织学分级均无关(均P>0.05);MEKK3与NF-κB蛋白的阳性表达呈正相关(r=0.308,P<0.05)。结论 MEKK3、NF-κB蛋白异常表达与食管鳞癌的发生、浸润转移及预后相关,且两者呈正相关。联合检测MEKK3和NF-κB蛋白表达可作为食管鳞癌的诊断、预后评估的参考依据。
Objective To study the expression of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3(MEKK3) and nuclear factor kappa B(NF-κ B) proteins in esophageal squamous cell carcinoma(ESCC) and their clinical significance.Methods The expression of MEKK3 and NF-κ B proteins in 76 cases of ESCC,35 cases of adjacent atypical hyperplasia tissues and 20 cases of normal tissue were detected by imnnunohistochemistry EnVision method.Results The positive rates of MEKK3 protein in ESCC tissue were significantly higher than those of atypical hyperplasia tissue and normal tissue(P<0.05).The positive rates of NF- k B protein were increased gradually in ESCC tissue,atypical hyperplasia tissue and normal tissue.In ESCC tissue,the positive expression of MEKK3 and NF- k B proteins was both correlated with the clinical stage,infiltration depth and lymph node metastasis(all P<0.05),but not correlated with age,sex,or degree of differentiation(all P >0.05).Expression of MEKK3 protein was positively associated with expression of NF- k B(r=0.308,P<0.05).Conclusion The expression of MEKK3 and NF- k B proteins can be used as a indicator for the diagnosis of ESCC and the prognosis of patients.
Objective To study the expression of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3(MEKK3) and nuclear factor kappa B(NF-κ B) proteins in esophageal squamous cell carcinoma(ESCC) and their clinical significance.Methods The expression of MEKK3 and NF-κ B proteins in 76 cases of ESCC,35 cases of adjacent atypical hyperplasia tissues and 20 cases of normal tissue were detected by imnnunohistochemistry EnVision method.Results The positive rates of MEKK3 protein in ESCC tissue were significantly higher than those of atypical hyperplasia tissue and normal tissue(P<0.05).The positive rates of NF- k B protein were increased gradually in ESCC tissue,atypical hyperplasia tissue and normal tissue.In ESCC tissue,the positive expression of MEKK3 and NF- k B proteins was both correlated with the clinical stage,infiltration depth and lymph node metastasis(all P<0.05),but not correlated with age,sex,or degree of differentiation(all P >0.05).Expression of MEKK3 protein was positively associated with expression of NF- k B(r=0.308,P<0.05).Conclusion The expression of MEKK3 and NF- k B proteins can be used as a indicator for the diagnosis of ESCC and the prognosis of patients.
引文
[1]Blank J L,Gerwins P,Elliott E M,et al.Molecular cloning of mitogen-activated protein/ERK kinase kinases(MEKK)2 and 3.Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase[J].J Biol Chem,1996,271(10):5361-5368.
[2]Shirakihara T,Horiguchi K,Miyazawa K,et al.TGF-p regulates isoform switching of FGF receptors and epithelial-mesenchymal transition[J].EMBO J,2011,30(4):783-795.
[3]Li W,Tan D,Zenali M J,et al.Constitutive activation of nuclear-factor-kappa B(NF-κB)signaling pathway in fibrolamellar hepatocellular carcinoma[J].Int J Clin Exp Pathol,2009,3(3):238-243.
[4]Yang J,Boerm M,Mccarty M,et al.MEKK3 is essential for early embryonic cardiovascular development[J].Nat Genet,2000,24(3):309-313.
[5]Huang Q,Yang J,Lin Y,et al.Differential regulation of interleukin 1receptor and Toll-like receptor signaling by MEKK3[J].Nat Immunol,2004,5(1):98-103.
[6]Yang J,Lin Y,Guo Z,et al.The essential role of MEKK3 in TNFinduced NF-kappa B activation[J].Nat Immunol,2001,2(7):620-624.
[7]金亦,邵春奎,唐录英,等.肝细胞癌中Survivin与NF-κB蛋白的表达及其临床意义[J].中华医学杂志,2011,91(36):2542-2545.
[8]Samanta A K,Huang H J,Le X F,et al.MEKK3 expression correlates with nuclear-factor-kappaB activity and with expression of antiapoptotic genes in serous ovarian carcinoma[J].Cancer,2009,115(17):3897-3908.
[9]Chiao P J,Na R,Niu J,et al.Role of Rel/NF-kappaB transcirption factors in apoptosis of human hepatocellular carcinoma cells[J].Cancer,2002,95(8):1696-1705.
[10]Lin S S,Lai K C,Hsu S C,et al.Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and-9 and vascular endothelial growth factor(VEGF)[J].Cancer Lett,2009,285(2):127-133.
[2]Shirakihara T,Horiguchi K,Miyazawa K,et al.TGF-p regulates isoform switching of FGF receptors and epithelial-mesenchymal transition[J].EMBO J,2011,30(4):783-795.
[3]Li W,Tan D,Zenali M J,et al.Constitutive activation of nuclear-factor-kappa B(NF-κB)signaling pathway in fibrolamellar hepatocellular carcinoma[J].Int J Clin Exp Pathol,2009,3(3):238-243.
[4]Yang J,Boerm M,Mccarty M,et al.MEKK3 is essential for early embryonic cardiovascular development[J].Nat Genet,2000,24(3):309-313.
[5]Huang Q,Yang J,Lin Y,et al.Differential regulation of interleukin 1receptor and Toll-like receptor signaling by MEKK3[J].Nat Immunol,2004,5(1):98-103.
[6]Yang J,Lin Y,Guo Z,et al.The essential role of MEKK3 in TNFinduced NF-kappa B activation[J].Nat Immunol,2001,2(7):620-624.
[7]金亦,邵春奎,唐录英,等.肝细胞癌中Survivin与NF-κB蛋白的表达及其临床意义[J].中华医学杂志,2011,91(36):2542-2545.
[8]Samanta A K,Huang H J,Le X F,et al.MEKK3 expression correlates with nuclear-factor-kappaB activity and with expression of antiapoptotic genes in serous ovarian carcinoma[J].Cancer,2009,115(17):3897-3908.
[9]Chiao P J,Na R,Niu J,et al.Role of Rel/NF-kappaB transcirption factors in apoptosis of human hepatocellular carcinoma cells[J].Cancer,2002,95(8):1696-1705.
[10]Lin S S,Lai K C,Hsu S C,et al.Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and-9 and vascular endothelial growth factor(VEGF)[J].Cancer Lett,2009,285(2):127-133.