Downregulation of p57 accelerates the growth and invasion of hepatocellular carcinoma
| Autor: | Yi Lv, Tao Tian, Ting Hua Hu, Lili Jiang, Zhi Ping Ruan, Hui Guo, Xin Sui, Ke Jun Nan, Wen Juan Wang |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Cancer Research Carcinoma Hepatocellular Cyclin E Down-Regulation Biology Mice Cyclin D1 Downregulation and upregulation Cell Line Tumor Animals Humans Neoplasm Invasiveness RNA Messenger Cyclin-Dependent Kinase Inhibitor p57 neoplasms Aged Mice Inbred BALB C Gene knockdown Reverse Transcriptase Polymerase Chain Reaction Cell growth Cyclin-dependent kinase 4 Liver Neoplasms Cyclin-dependent kinase 2 General Medicine Middle Aged Immunohistochemistry digestive system diseases biology.protein Cancer research Female Cell Division |
| Zdroj: | Carcinogenesis. 32:1897-1904 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgr220 |
| Popis: | p57 is a multifunctional protein involved in the regulation of tumor formation and development; however, the biological role of p57 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. To explore the role of p57 in the development of HCC, we examined p57 messenger RNA (mRNA) and protein levels in HCC tissues and adjacent non-cancerous tissues by immunohistochemistry, real-time polymerase chain reaction and western blot analysis. Moreover, we generated stable p57 knockdown HCC cell lines to investigate the impact of p57 downregulation on the growth and invasion of HCC in vitro and in vivo. Our results showed that p57 mRNA and protein levels were significantly decreased in human HCC tissues. In addition, this reduction in p57 expression was associated with increased tumor size, more advanced TNM stages, the presence of capsule invasion and extrahepatic metastasis and decreased overall survival time. In human HCC cell lines, p57 downregulation increased the expression of cyclin D1 and CDK2 and enhanced the activities of CDK4/cyclin D1 and CDK2/cyclin E complexes, resulting in increased cellular proliferation and growth of xenografts. Furthermore, p57 downregulation accelerated the invasion of HCC cells in vitro and in vivo by controlling the activity of LIMK1. In conclusion, the downregulation of p57 accelerates the growth and invasion of HCC, indicating that p57 is an important tumor suppressor in HCC. Based on these findings, p57 may be a potential target for HCC prevention and therapy. |
| Databáze: | OpenAIRE |
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