Tai D I, Tsai S L, Chang Y H, Huang S N, Chen T C, Chang K S, Liaw Y F
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan, Republic of China.
Cancer. 2000 Dec 1;89(11):2274-81.
Nuclear factor kappaB (NF-kappaB) is a transcription factor that plays important roles in cell proliferation and in immunity against viral infections. NF-kappaB is a dimer of Rel proteins that is sequestered in the cytoplasm as an inactive form through interaction with an inhibitory kappaB (IkappaB) protein. When IkappaB is degraded, the NF-kappaB dimer will enter the nucleus to activate the target genes. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may activate NF-kappaB and, thus, may modulate cell apoptosis and may be associated with oncogenesis. The role of NF-kappaB in hepatocellular carcinoma (HCC) has not yet been explored.
Immunohistochemical staining to search for active nuclear RelA and nuclear IkappaBalpha proteins were done on formalin fixed liver tissues from 65 patients with HCC and from 9 normal control participants. Nuclear extracts of fresh-frozen tumor and nontumor liver tissues from 37 patients with HCC and from 7 normal controls were tested for NF-kappaB-DNA binding activity by electrophoretic mobility shift assay. The RelA and IkappaBalpha protein expressions were studied by Western blot analysis.
Nuclear NF-kappaB stainings were significantly more abundant in HBV-infected or HCV-infected tumors as well as nontumor parts of HCC compared with normal controls. Nuclear NF-kappaB DNA binding activity and nuclear RelA protein expression were greater in tumor tissue compared with nontumor tissue, whereas cytosolic IkappaBalphs protein expression was generally greater in nontumor tissue compared with tumor tissue.
Constitutive activation of NF-kappaB was found more frequently in tumor tissue compared with nontumor tissue. It is possible that NF-kappaB overexpression accompanied by dysregulation of IkappaBalpha may play a role in the hepatocarcinogenesis of HBV or HCV infection.
核因子κB（NF-κB）是一种转录因子，在细胞增殖和抗病毒感染免疫中发挥重要作用。NF-κB是Rel蛋白的二聚体，通过与抑制性κB（IkappaB）蛋白相互作用以无活性形式隔离于细胞质中。当IkappaB降解时，NF-κB二聚体将进入细胞核以激活靶基因。慢性乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染可能激活NF-κB，从而可能调节细胞凋亡，并可能与肿瘤发生有关。NF-κB在肝细胞癌（HCC）中的作用尚未得到探索。
对65例HCC患者和9名正常对照者的福尔马林固定肝组织进行免疫组织化学染色，以检测活性核RelA和核IkappaBalpha蛋白。通过电泳迁移率变动分析检测37例HCC患者和7名正常对照者的新鲜冷冻肿瘤和非肿瘤肝组织的核提取物中的NF-κB-DNA结合活性。通过蛋白质免疫印迹分析研究RelA和IkappaBalpha蛋白表达。
与正常对照相比，HBV感染或HCV感染的肿瘤以及HCC的非肿瘤部分中核NF-κB染色明显更丰富。与非肿瘤组织相比，肿瘤组织中的核NF-κB DNA结合活性和核RelA蛋白表达更高，而与肿瘤组织相比，非肿瘤组织中的细胞质IkappaBalphs蛋白表达通常更高。
与非肿瘤组织相比，肿瘤组织中更频繁地发现NF-κB的组成性激活。NF-κB过表达伴IkappaBalpha失调可能在HBV或HCV感染的肝癌发生中起作用。
