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Annals of Surgical Oncology
Erschienen in: Annals of Surgical Oncology 12/2013

01.11.2013 | Translational Research and Biomarkers

The E2F Transcription Factor 1 Transactives Stathmin 1 in Hepatocellular Carcinoma

verfasst von: Yi-Ling Chen, MS, Yih-Huei Uen, MD, Chien-Feng Li, MD, Kuo-Chan Horng, MS, Lih-Ren Chen, PhD, Wen-Ren Wu, MS, Hong-Yu Tseng, MS, Hsuan-Ying Huang, MD, Li-Ching Wu, PhD, Yow-Ling Shiue, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 12/2013

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.
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Metadaten
Titel
The E2F Transcription Factor 1 Transactives Stathmin 1 in Hepatocellular Carcinoma
verfasst von
Yi-Ling Chen, MS
Yih-Huei Uen, MD
Chien-Feng Li, MD
Kuo-Chan Horng, MS
Lih-Ren Chen, PhD
Wen-Ren Wu, MS
Hong-Yu Tseng, MS
Hsuan-Ying Huang, MD
Li-Ching Wu, PhD
Yow-Ling Shiue, PhD
Publikationsdatum
01.11.2013
Verlag
Springer US
Erschienen in
Annals of Surgical Oncology / Ausgabe 12/2013
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2519-8

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