Targeted disruption of S100P suppresses tumor cell growth by down-regulation of cyclin D1 and CDK2 in human hepatocellular carcinoma
Targeted disruption of S100P suppresses tumor cell growth by down-regulation of cyclin D1 and CDK2 in human hepatocellular carcinoma
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DOI：
10.3892/ijo_00000442
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发表时间：
2009-12-01
影响因子：
5.2
通讯作者：
Nam, Suk Woo
中科院分区：
文献类型：
--
作者：
Kim, Jeong Kyu;Jung, Kwang Hwa;Nam, Suk Woo
肝细胞癌是全球第三大癌症死亡原因。近几十年来，肝细胞癌的病例数量持续增加。以往的研究表明，S100P是S100P钙结合蛋白家族中的一员，在一些恶性肿瘤中存在异常调控。然而，S100P调控失调的潜在分子机制仍有待阐明。为探讨S100P在肝癌发生中的生物学作用，采用免疫组织化学(IHC)、Western印迹分析和逆转录聚合酶链式反应(RT-PCR)检测了S100P在肝癌组织和细胞系中的异常表达。人肝癌细胞株Hep3B中S100P的内源性表达被RNA干扰蛋白敲除方法干扰。比较siRNA转染组和对照组的细胞生长和细胞凋亡率。用Western印迹法检测S100P沉默对细胞周期调控主要成分的影响。结果表明，肝细胞癌组织中S100P水平明显高于相应的正常组织。靶向阻断S100P可抑制细胞生长，促进细胞凋亡。此外，抑制S100P还导致细胞周期蛋白1和细胞周期蛋白CDK2表达下调。综上所述，本研究显示S100P在肝细胞癌中高表达。S100P在肝细胞癌中的异常调控可能激活了细胞周期蛋白D1和CDK的表达，并参与了肝癌发生过程中肿瘤细胞的有丝分裂潜能。这些发现为肝癌的治疗提供了新的治疗策略。
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The number of cases of HCC has continued to increase in recent decades. Previous studies have suggested that S100P, a member of the S100P calcium-binding protein family, is aberrantly regulated in several malignant neoplasms. However, the underlying molecular mechanisms of the dysregulation of S100P remain to be elucidated. To investigate biological effects of S100P on hepatocarcinogenesis, aberrant expression of S100P was investigated by immunohistochemistry (IHC), Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) in HCC tissues and cell lines. Endogenous expression of S100P was disrupted by the RNA interference-mediated protein knockdown method in the human Hep3B liver cancer cell line. Then, cell growth and cellular apoptosis were compared with control siRNA transfectants. The effects of S100P-silencing on the major components of cell cycle regulation were assessed by Western blot analysis. As results, elevated levels of S100P were observed in the HCC tissues compared to the corresponding normal tissues. Targeted disruption of S100P suppressed cell growth and augmented cellular apoptosis. In addition, inhibition of S100P resulted in the down-regulation of cyclinD1 and CDK2. In conclusion, this study showed over-expression of S100P in HCC. The aberrant regulation of S100P in HCC might activate cyclin D1 and CDK expression and contribute to the mitogenic potential of tumor cells during HCC carcinogenesis. These findings provide information that suggests new therapeutic strategies for the treatment of liver cancer.