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Proteome analysis in normal liver, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma-For a novel diagnosis, treatment and protection of hepatocellular carcinoma

正常肝脏、慢性肝炎、肝硬化和肝细胞癌的蛋白质组分析-肝细胞癌的新诊断、治疗和保护

基本信息

批准号：
15590654
负责人：
MASAKI Tsutomu
金额：
$ 2.24万
依托单位：
Kagawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590654/
关键词：
hepatocllular carcinoma cell cycle Cdk Cdk inhibitor p18^<INK4C>LECラット

项目摘要

Cyclins, cyclin-dependent kinases (Cdks), and Cdk inhibitors (CdkIs) are frequently altered in human cancer. p 18^<INK4C>, a member of the INK4 family among CdkIs, is a potential tumor suppressor gene product. However, the expression of p 18^<INK4C> in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to examine the expression of p18^<INK4C> in various liver diseases including HCC and to assess its clinical significance in HCC. To that end, we examined the expression of p 18^<INK4C> by immunohistochemistry in various liver diseases including 51 HCCs, and also studied the relationship among p 18^<INK4C> expression, the phosphorylation of retinoblastoma protein (pRb), and the activity level of Cdk4 and Cdk6. Immunohistochemical analysis revealed the frequent loss of p18^<INK4C> expression in HCC, especially in poorly differentiated HCC. The loss of p18^<INK4C> expression was shown to be associated with a poor prognosis as compared with that associated with p18^<INK4C>-positivity. Further, the kinas activity of Cdk4 was found to be higher in p18^<INK4C>-negative HCCs than in p 18^<INK4C>-positive HCCs. However, the level of Cdk6 activity was similar in the two groups of HCCs. In p18^<INK4C>-positive HCCs, p18^<INK4C> dominantly interacted with Cdk4 rather than with Cdk6. pRb phosphorylated at Ser 780 was detected more frequently in p18^<INK4C>-negative than in p 18^<INK4C>-positive HCCs. These data suggest that the loss of p18^<INK4C> expression may play a role in the differentiation and development of HCC through the upregulation of Cdk4 activity.

细胞周期蛋白、细胞周期蛋白依赖性激酶（Cdks）和Cdk抑制剂（CdkIs）在人类癌症中经常改变。p18 β<INK4C>是CdkIs中INK 4家族的成员，是一种潜在的肿瘤抑制基因产物。然而，p18在<INK4C>肝细胞癌（HCC）中的表达尚不清楚.本研究的目的是检测p18^<INK4C>在包括肝癌在内的各种肝脏疾病中的表达，并评估其在肝癌中的临床意义。为此，我们通过免疫组织化学方法检测了<INK4C>包括51例HCC在内的各种肝脏疾病中p18 ^的表达，并研究了p18 ^<INK4C>表达、视网膜母细胞瘤蛋白（pRb）磷酸化以及Cdk 4和Cdk 6活性水平之间的关系。免疫组化结果显示p18 ~+<INK4C>在HCC中表达缺失，尤其是低分化HCC。与p18 <INK4C>^ -阳性相关者相比，p18^-表达缺失与不良预后相关<INK4C>。此外，发现p18^ -阴性HCC中Cdk 4激酶活性<INK4C>高于p18 ^<INK4C>-阳性HCC。然而，Cdk 6活性水平在两组HCC中相似。在p18^<INK4C>阳性的HCC中，p18^<INK4C>主要与Cdk 4而不是Cdk 6相互作用。p18^ -阴性HCC中pRb的Ser 780磷酸化频率高于<INK4C>p18 ^<INK4C>-阳性HCC。这些数据表明，p18 ~+表达的缺失<INK4C>可能通过上调Cdk 4活性在HCC的分化和发展中起作用。