Wang Zhao-wen, Peng Zhi-hai, Tang Hua-mei, Qiu Guo-qiang, Xing Tong-hai, Yang Ming-zhi
Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
Zhonghua Yi Xue Za Zhi. 2004 Feb 2;84(3):225-8.
To study the relation between the expression of p16 protein and Rb (retinoblastoma) protein and the transcription activity of nuclear factor-kappaB (NF-kappaB) and their roles in hepatocarcinogenesis.
p16 protein and Rb protein in 35 hepatocellular carcinoma (HCC) tissues and the peritumoral areas (more than 3 cm away from the tumor) were examined by Western blot analysis. The transcription activity of NF-kappaB in these tissues was detected by electrophoretic mobility shift assays (EMSA) and super-shift assays.
The expression rates of p16 protein in the HCC tissues and peritumoral areas were 37% (13/35) and 48% (17/35) respectively (P < 0.01). The expression rates of Rb protein in the HCC tissues and peritumoral areas were 34% (12/35) and 74% (26/35) respectively (P < 0.01). The emergence rates of NF-kappaB with transcription activity in the HCC tissues and peritumoral areas were 77% (27/35) and 85% (30/35) respectively (P > 0.05). Four out of the 10 (40%) HCC tissues expressing p16 protein and Rb protein simultaneously turned up NF-kappaB with transcription activity, while 18 out of the 20 (90%) HCC tissues not expressing both p16 and Rb proteins turned up NF-kappaB with transcription activity (P < 0.05). 13 out of the 17 (76%) peritumoral areas expressing two kinds of proteins simultaneously turned up NF-kappaB with transcription activity and the emergence rate of NF-kappaB with transcription activity in the peritumoral areas not expressing the two kinds of proteins was 89% (8/9) (P > 0.05).
Dysfunction of p16 is the early event of hepatocarcinogenesis and dysfunction of Rb is the later event in this course. There is a positive correlation between p16 protein and Rb protein in HCC tissues. The loss of expression of p16 and Rb proteins plays important roles in the carcinogenesis and progression of HCC by affecting NF-kappaB transcription activity which may prevent hepocyctes from apoptosis, besides disturbing cell cycle.
研究p16蛋白和Rb（视网膜母细胞瘤）蛋白的表达与核因子-κB（NF-κB）转录活性之间的关系及其在肝癌发生中的作用。
采用蛋白质免疫印迹法检测35例肝细胞癌（HCC）组织及其癌旁组织（距肿瘤边缘3 cm以外）中p16蛋白和Rb蛋白的表达。采用电泳迁移率变动分析（EMSA）和超迁移分析检测这些组织中NF-κB的转录活性。
HCC组织和癌旁组织中p16蛋白的表达率分别为37%（13/35）和48%（17/35）（P<0.01）。HCC组织和癌旁组织中Rb蛋白的表达率分别为34%（12/35）和74%（26/35）（P<0.01）。HCC组织和癌旁组织中具有转录活性的NF-κB出现率分别为77%（27/35）和85%（30/35）（P>0.05）。10例（40%）同时表达p16蛋白和Rb蛋白的HCC组织中有4例出现具有转录活性的NF-κB，而20例（90%）未同时表达p16和Rb蛋白的HCC组织中有18例出现具有转录活性的NF-κB（P<0.05）。17例（76%）同时表达两种蛋白的癌旁组织中有13例出现具有转录活性的NF-κB，未表达这两种蛋白的癌旁组织中具有转录活性的NF-κB出现率为89%（8/9）（P>0.05）。
p16功能异常是肝癌发生的早期事件，Rb功能异常是该过程中的晚期事件。HCC组织中p16蛋白与Rb蛋白之间存在正相关关系。p16和Rb蛋白表达缺失通过影响NF-κB转录活性在HCC的发生和发展中起重要作用，这可能除了扰乱细胞周期外，还能阻止肝细胞凋亡。
