Plkl与p21WAF1/CIP1在肝细胞癌中的表达

李辉; 张婷; 鲁凤民; 徐春晖; 唐芙爱; 陈香梅; 马军

Plkl与p21WAF1/CIP1在肝细胞癌中的表达

1. 郑州大学第二附属医院消化内科
2. 北京大学医学部病原生物学系

基金项目:

国家自然科学基金资助项目(30771099)； “艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“十一五”计划项目(2009ZX10004-903)；

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中图分类号: R735.7
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出版历程
- 出版日期: 2011-04-20

Associated expression of Plkl and p21WAF1/CIP1 in hepatocellular carcinoma

Research funding:

摘要

摘要: 目的细胞周期抑制因子p21WAF1/CIP1（p21）可在转录水平抑制Polo-like kinase1（Plk1）基因的表达,本文旨在探讨Plk1和p21蛋白在肝细胞癌中的表达及相关性。方法应用Western Blot方法检测10对原发性肝细胞癌和癌旁组织中Plk1和p21蛋白的表达情况。通过将pFlex-p21表达质粒瞬时转染人肝癌细胞系HepG2细胞,进一步检测p21过表达对Plk1mRNA和蛋白表达的影响。结果 Plk1在10例肝癌组织中的表达均高于配对癌旁组织,p21蛋白在7对肝癌组织中的表达高于配对癌旁组织。HepG2细胞瞬时表达p21质粒后,Plk1的蛋白表达和mRNA水平均无变化（P>0.05）。结论 Plk1和p21在肝细胞癌组织中的表达具有一定的肿瘤特异性。肝癌组织中p21蛋白过表达可能不具有抑制Plk1表达的作用,具体机制还有待于进一步研究。
- 癌,肝细胞 /
- 基因表达 /
- 细胞周期蛋白类 /
- 肿瘤抑制蛋白质类 /
- 原癌基因蛋白质类
Abstract: Objective It has been shown that the cell cycle inhibitor p21WAF1/CIP1 (p21) can lead to the transcriptional inhibition of the Polo-like kinase 1 (Plk1) gene, this study was aimed to investigate the expression of Plk1 and p21 genes in hepatocellular carcinoma (HCC) and to explore the expression correlations between the two genes.Methods Expression of Plkl and p21 protein was evaluated separately by Western Blot in 10 surgically resected HCCs with HBV infection.pFlex-p21 vector was transfected into liver cancer cell line HepG2, and the changes of Plk1 mRNA expression and protein expression were detected using RT-PCR and Western-blot analysis respectively.Results The expression of Plk1 was higher in the HCC tissues than in the corresponding non-tumorous liver tissue in all samples tested, increased p21expression in HCC was found in 7 of 10 paired tissues, as determined by Western-blot.In consistent to our observation in preliminary tumor tissues, in vitro study via ectopic p21 over expression in HepG2 cells failed to suppress Plk1 gene expression in either transcriptional or protein levels (P>0.05) .Conclusion Increased Plk1 and p21 expression may associate to the hepatocarcinogenesis in HCC patients with HBV infection.Different from the previous reports, our data showed that at least in those HCCs with HBV infection, p21 may not inhibit Plk1 expression.The mechanisms of Plk1overexpression in HCC need further research.
- carcinoma /
- hepatocellular /
- gene expression /
- cyclins /
- turnor suppressor proteins

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参考文献(16)

[1]Sumara I, Giménez-Abián JF, Gerlich D, et al.Rolesof polo-like kinase 1 in the assembly of functional mitoticspindles[J].Curr Biol, 2004, 14 (19) :1712-1722.

[2]Golsteyn RM, Mundt KE, Fry AM, et al.Cell cycle regulationof the activity and subcellular localization of Plk1, a humanprotein kinase implicated in mitotic spindle function[J].J CellBiol, 1995, 129 (6) :1617-1628.

[3]Zhao C, Gong L, Li W, et al.Overexpression of Plk1 promotesmalignant progress in human esophageal squamous cellcarcinoma[J].J Cancer Res Clin Oncol, 2010, 136 (1) :9-16.

[4]Lan B, Liu BY, Chen XH, et al.Polo like kinase 1 expressionand prognostic value in gastric carcinomas[J].ZhonghuaWeichang Waike Zazhi, 2007, 10 (1) :70-72.

[5]He ZL, Zheng H, Lin H, et al.Overexpression of polo-likekinase1 predicts a poor prognosis in hepatocellular carcinomapatients[J].World J Gastroenterol, 2009, 15 (33) :4177-4182.

[6]Takahashi T, Sano B, Nagata T, et al.Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers[J].Cancer Sci, 2003, 94 (2) :148-152.

[7]Zhang J, Wang S, Kern S, et al.Nitric oxide down-regulatespolo-like kinase 1 through a proximal promoter cell cycle genehomology region[J].J Biol Chem, 2007, 282 (2) :1003-1009.

[8]Zhu H, Chang BD, Uchiumi T, et al.Identification of promoterelements responsible for transcriptional inhibition of polo-likekinase 1 and topoisomerase IIalpha genes by p21 (WAF1/CIP1/SDI1) [J].Cell Cycle, 2002, 1 (1) :59-66.

[9]鲁凤民, 李雅娟, 庄辉.N-端加flag标签增加P21 (Cip1/WAF1) 蛋白质稳定性[J].癌变.畸变.突变, 2006, 18 (2) :119-121.

[10]Degenhardt Y, Lampkin T.Targeting Polo-like kinase incancer therapy[J].Clin Cancer Res, 2010, 16 (2) :384-389.

[11]Takaki T, Trenz K, Costanzo V, et al.Polo-like kinase 1 reachesbeyond mitosis--cytokinesis, DNA damage response, anddevelopment[J].Curr Opin Cell Biol, 2008, 20 (6) :650-660.

[12]Pellegrino R, Calvisi DF, Ladu S, et al.Oncogenic and tumorsuppressive roles of polo-like kinases in human hepatocellularcarcinoma[J].Hepatology, 2010, 51 (3) :857-868.

[13]Zhang MF, Zhang ZY, Fu J, et al.Correlation betweenexpression of p53, p21/WAF1, and MDM2 proteins andtheir prognostic significance in primary hepatocellularcarcinoma[J].J Transl Med, 2009, 7 (1) :110-118.

[14]Mitselou A, Karapiperides D, Nesseris I, et al.Alteredexpression of cell cycle and apoptotic proteins in human liverpathologies[J].Anticancer Res, 2010, 30 (11) :4493-4501.

[15]Park US, Park SK, Lee YI, et al.Hepatitis B virus-X proteinupregulates the expression of p21waf1/cip1 and prolongsG1-S transition via a p53-independent pathway in humanhepatoma cells[J].Oncogene, 2000, 19 (30) :3384-3394.

[16]Kobayashi S, Matsushita K, Saigo K, et al.P21WAF1/CIP1messenger RNA expression in hepatitis B, C virus-infectedhuman hepatocellular carcinoma tissues[J].Cancer, 2001, 91 (11) :2096-2103.

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