The E2F Transcription Factor 1 Transactives Stathmin 1 in Hepatocellular Carcinoma
Autor: | Li-Ching Wu, Yow-Ling Shiue, Yi Ling Chen, Chien Feng Li, Hong-Yu Tseng, Lih-Ren Chen, Yih-Huei Uen, Wen-Ren Wu, Kuo-Chan Horng, Hsuan-Ying Huang |
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Rok vydání: | 2012 |
Předmět: |
Male
Pathology Immunoenzyme Techniques Tumor Cells Cultured Microarray databases RNA Small Interfering Luciferases Promoter Regions Genetic Reverse Transcriptase Polymerase Chain Reaction Cell Cycle Liver Neoplasms Cell cycle Flow Cytometry Prognosis humanities Gene Expression Regulation Neoplastic Liver Oncology Hepatocellular carcinoma Female alpha-Fetoproteins Transcription Factor DP1 Transcriptional Activation Chromatin Immunoprecipitation medicine.medical_specialty Carcinoma Hepatocellular Blotting Western education Real-Time Polymerase Chain Reaction Downregulation and upregulation Carcinoma medicine Humans RNA Messenger E2F neoplasms Transcription factor Cell Proliferation Neoplasm Staging Retrospective Studies business.industry HCCS medicine.disease digestive system diseases Mutation Mutagenesis Site-Directed Cancer research Stathmin Surgery business E2F1 Transcription Factor Follow-Up Studies |
Zdroj: | Annals of Surgical Oncology. 20:4041-4054 |
ISSN: | 1534-4681 1068-9265 |
Popis: | Through data mining the Stanford Microarray Database, the stathmin 1 (STMN1) transcript was found to be frequently upregulated in the hepatocellular carcinoma (HCC) with low alpha-fetoprotein level. The molecular mechanism of STMN1 upregulation in HCCs remained unclear.Quantitative RT-PCR, immunoblotting, immunohistochemistry, and transfection of expression or small hairpin RNA interference plasmids, chromatin immunoprecipitation (ChIP), and quantitative ChIP assays were performed in HCC specimens or 2 distinct HCC-derived cell lines. Dual luciferase assay and site-directed mutagenesis were applied to analyze the activities of STMN1 proximal promoter region.STMN1 mRNA and proteins were significantly associated with several clinicopathological features. High STMN1 or E2F1 immunoexpression was predictive of poor overall survival (OS) rate (P.01). In HCC-derived cell lines, E2F1 was elevated before STMN1 mRNA during the cell cycle. Exogenous expression of E2F1 or both transcription factor DP-1 (TFDP1) and E2F1 genes induced E2F1 and STMN1 mRNA (P.01). Knockdown of the E2F1 gene suppressed E2F1 and STMN1 mRNA and E2F1 and STMN1 protein levels (P.05). The promoter activity of STMN1 gene increased with overexpression of both E2F1 and TFDP1 genes (P.05); however, it decreased when mutations were introduced in the E2F1-binding sites (P.05).Upregulation of E2F1 and STMN1 proteins associate with worse outcomes in patients with HCC. E2F1 significantly correlates with STMN1 protein level in HCC lesions and in vitro transactivation assays, suggesting that STMN1 gene is transactivated by the E2F1 protein. |
Databáze: | OpenAIRE |
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