Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 7, 2011; 17(29): 3420-3430
Published online Aug 7, 2011. doi: 10.3748/wjg.v17.i29.3420
Late SV40 factor: A key mediator of Notch signaling in human hepatocarcinogenesis
Ren-Hua Fan, Jing Li, Nan Wu, Ping-Sheng Chen
Ren-Hua Fan, Jing Li, Nan Wu, Ping-Sheng Chen, Department of Pathology, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
Author contributions: Fan RH, Li J and Wu N contributed equally to this work and performed the majority of experiments; Chen PS performed the diagnoses of liver cancer tissue specimens; Fan RH and Chen PS designed the study and wrote the manuscript.
Supported by The National Natural Science Foundation of China, No. 30470780
Correspondence to: Ping-Sheng Chen, Professor, Department of Pathology, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China. chenps@seu.edu.cn
Telephone: +86-25-83272507 Fax: +86-25-83324887
Received: November 22, 2010
Revised: February 26, 2011
Accepted: March 5, 2011
Published online: August 7, 2011
Abstract

AIM: To investigate the relationship between late SV40 factor (LSF) and Notch signaling in the development and progress of hepatocellular carcinoma (HCC).

METHODS: Liver cancer tissue specimens from 25 patients were analyzed for Notch-1 and LSF expression by immunohistochemistry. The correlation between expression and the biological effects of Notch-1 and LSF were analyzed using genetic and pharmacological strategies in HCC cell lines and human normal cell lines, including hepatic stellate cells (HSC) and human embryonic kidney epithelial cells (HEK).

RESULTS: Immunohistochemistry showed that both Notch-1 and LSF were significantly upregulated in HCC samples (76%, 19/25, P < 0.0001 and 84%, 21/25, P < 0.0001, respectively) compared with non-cancer samples. Activation of Notch-1 by exogenous transfection of Notch1 intracellular domain increased LSF expression in HSC and HEK cells to levels similar to those seen in HepG2 cells. Furthermore, blocking Notch-1 activation with a γ-secretase inhibitor, DAPT, downregulated LSF expression in HepG2 cells. Additionally, a biological behavior assay showed that forced overexpression of LSF promoted HepG2 cell proliferation and invasion.

CONCLUSION: LSF is a key mediator of the Notch signaling pathway, suggesting that it might be a novel therapeutic target for the treatment of HCC.

Keywords: Notch receptor; Late SV40 factor; Signal transduction; Hepatocellular carcinoma