Activation of NF-kappaB, AP-1 and STAT transcription factors is a frequent and early event in human hepatocellular carcinomas
Activation of NF-kappaB, AP-1 and STAT transcription factors is a frequent and early event in human hepatocellular carcinomas
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DOI：
10.1016/s0168-8278(02)00064-8
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发表时间：
2002-07-01
影响因子：
25.7
通讯作者：
Bernuau, D
中科院分区：
文献类型：
--
作者：
Liu, P;Kimmoun, E;Bernuau, D
背景/目标：已显示两种肝癌诱导物B和C型肝炎病毒在体外激活AP-1、NF-κ B和STAT，但尚未提供关于这些转录因子在体内的活性的详细信息。我们已经测量了15个原发性肝癌的肿瘤周围和肿瘤部分中这些转录因子的DNA结合活性，这些原发性肝癌有病毒或非病毒病因，结果：AP-1、NF-κ B和STAT结合活性在癌周组织中分别有73%、87%和70%的病例高于组织学正常肝脏。在40%和80%的病例中，分别检测到AP-1、NF-κ B的进一步活化，但在肿瘤部分未检测到STAT结合。在肿瘤阶段，发现JunD和c-Jun水平与AP-1结合活性之间存在密切相关性。相比之下，AP-1和NF-κ B结合活性低或仅略有升高，在肿瘤周围和肿瘤组织的transferations.Conclusions：AP-1，NF-κ B和STAT的早期激活可能有助于收购的转化表型在肝癌发生过程中，无论病因。(C)2002年欧洲肝脏研究协会。由Elsevier Science B. V.出版，版权所有。
Background/Aims: Hepatitis B and C viruses, two inducers of hepatocarcinomas, have been shown to activate AP-1, NF-kappaB and STAT in vitro, but no detailed information on the activity of these transcription factors in vivo have been provided.Methods: We have measured the DNA binding activity of these transcription factors in the peri-tumoral and the tumoral parts of 15 primary liver cancers, of viral or non-viral etiologies, and in five hepatic metastases using electrophoretic mobility shift assays.Results: AP-1, NF-kappaB and STAT binding activities were increased in the peritumoral tissue, compared with histologically normal livers in 73, 87 and 70%, respectively, of the cases. A further activation of AP-1, NF-kappaB, but not STAT binding in the tumoral parts was detected in 40 and 80%, respectively, of the cases. A close correlation was found between JunD and c-Jun levels and AP-1 binding activity at the tumoral stage. By contrast, AP-1 and NF-kappaB binding activities were low or only slightly elevated in the peri-tumoral and the tumoral tissue of metastases.Conclusions: Early activation of AP-1, NF-kappaB and STAT contributes probably to the acquisition of a transformed phenotype during hepatocarcinogenesis, whatever the etiology. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.