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
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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