Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas

被引:82
作者
Azechi, H
Nishida, N
Fukuda, Y
Nishimura, T
Minata, M
Katsuma, H
Kuno, M
Ito, T
Komeda, T
Kita, R
Takahashi, R
Nakao, K
机构
[1] Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Sakyo Ku, Kyoto 6068507, Japan
[3] Kyoto Univ, Coll Med Technol, Kyoto, Japan
关键词
hepatocellular carcinoma; p16; retinoblastoma protein; cyclin D1; p16/cyclin D1/retinoblastoma protein pathway;
D O I
10.1159/000058531
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
p16, cyclin D1 and retinoblastoma protein (pRB) regulate G(1) to S transition and are commonly targeted in various cancers. However, few studies have simultaneously examined all components of the p16/cyclin D1/pRB pathway (RB pathway) in hepatocellular carcinoma (HCC). To clarify the role of the disruption of the RE pathway in HCC, we analyzed p16, pRB and cyclin D1 in 47 HCCs. Inactivation of p16 was detected in 30 of 47 HCCs (64%) by Western blot analysis and significantly correlated with hypermethylation of the promoter of this gene. pRB expression was found to be absent in 13 of 47 HCCs (28%) by immunohistochemistry. We found that 38 of 47 HCCs (81%) contained at least one inactivation in either PRE or p16. Furthermore, there was a significant inverse correlation between p16 and pRB inactivation (p = 0.041). Overexpression of cyclin D1 was detected in 5 of 47 HCCs (11%) by immunohistochemistry. The cases with cyclin D1 overexpression exhibited an advanced clinicopathological appearance and also contained inactivation of PRE and/or p16. These findings suggest that inactivation of pRB and/or p16 is a major event in human hepatocarcinogenesis, while cyclin D1 overexpression may confer additional growth advantages to the tu mor in addition to PRE and/or p16 inactivation in HCC. Copyright (C) 2001 S. Karger AG, Basel.
引用
收藏
页码:346 / 354
页数:9
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