Alteration of the p14ARF gene and p53 status in human hepatocellular carcinomas
Alteration of the p14ARF gene and p53 status in human hepatocellular carcinomas
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DOI：
10.1007/s00535-003-1302-9
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发表时间：
2004-04-01
影响因子：
6.3
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Ito, T;Nishida, N;Nakao, K
背景资料。INK4a/ARF基因编码p16(INK4a)和p14(ARF)，这两个基因对视网膜母细胞瘤(Rb)/p16(INK4a)和p53/ARF这两条抑癌通路至关重要。Rb/p16(INK4a)基因失活的报道很多，但对日本人肝细胞癌中p14(ARF)基因的改变还缺乏足够的分析。方法：研究方法。为探讨P53/ARF基因改变在肝癌发生中的作用，我们检测了44例肝癌组织中p14(ARF)基因的mRNA表达、缺失、突变和启动子高甲基化情况，并分析了同一系列肝癌中P53基因的改变。结果。1例肝细胞癌存在外显子1β至外显子2的纯合子缺失，2例肝细胞癌发生外显子2内突变，但未发现启动子高甲基化。3例p14(ARF)改变的肝细胞癌均分化良好。44例肝细胞癌中有12例(27.2%)有P53蛋白表达，而P53蛋白表达阳性的肿瘤中只有1例分化良好。TaqMan聚合酶链式反应结果显示，p14(ARF)在肝癌组织中的表达明显高于相应的非肿瘤组织(P
Background. The INK4a/ARF locus encodes p16(INK4a) and p14(ARF), both of which are crucial for two tumor suppressor pathways, retinoblastoma (RB)/p16(INK4a), and p53/ARF. Inactivation of RB/p16(INK4a), was frequently reported, but alterations of the p14(ARF) gene in hepatocellular carcinoma (HCC) in the Japanese population have been insufficiently analyzed. Methods. To determine the role of p53/ARF alteration in hepatocarcinogenesis, we examined 44 HCCs for mRNA expression, deletion, mutation, and promoter hypermethylation of the p14(ARF) genes alterations of p53 were also analyzed in the same series of HCCs. Results. Homozygous deletion, spanning from exon 1beta to exon 2, was found in 1 HCC mutations within exon 2 were found in 2 HCCs, but no promoter hypermethylation was detected. All 3 HCCs with p14(ARF) alteration were well differentiated. Twelve of the 44 HCCs (27.2%) showed immunohistochemical evidence of p53 alterations however, only 1 of the tumors with p53 alteration was well differentiated. TaqMan polymarase chain reaction (PCR) indicated that the expression of p14(ARF) in HCCs was higher than in that in all but three of the corresponding non-tumorous tissues (P