Next Article in Journal
Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer
Next Article in Special Issue
Cystic Fibrosis Related Liver Disease—Another Black Box in Hepatology
Previous Article in Journal
DADS Suppresses Human Esophageal Xenograft Tumors through RAF/MEK/ERK and Mitochondria-Dependent Pathways
Previous Article in Special Issue
Impact of Serum Chemerin Levels on Liver Functional Reserves and Platelet Counts in Patients with Hepatocellular Carcinoma
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2014, 15(7), 12442-12457; doi:10.3390/ijms150712442

Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells

1
Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
2
Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
3
Translational Research Center, Cancer Center, Department of Medical Research, and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
4
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70456, Taiwan
5
Drug Discovery and Development Center, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 7 April 2014 / Revised: 19 June 2014 / Accepted: 20 June 2014 / Published: 14 July 2014
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
View Full-Text   |   Download PDF [2827 KB, uploaded 14 July 2014]   |  

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Previous studies have noted the induction of endoplasmic reticulum stress or apurinic endonuclease 1 (APE1) expression in many tumors. Therefore, the aim of this study was to investigate the relationship between endoplasmic reticulum (ER stress) and APE1 in hepatocellular carcinoma. Here we investigate the expression of APE1 during ER stress in HepG2 and Huh-7 cell lines. Tunicamycin or brefeldin A, two ER stress inducers, increased APE1 and GRP78, an ER stress marker, expression in HepG2 and Huh-7 cells. Induction of APE1 expression was observed through transcription level in response to ER stress. APE1 nuclear localization during ER stress was determined using immunofluorescence assays in HepG2 cells. Furthermore, expression of Hepatitis B virus pre-S2∆ large mutant surface protein (pre-S2∆), an ER stress-induced protein, also increased GRP78 and APE1 expression in the normal hepatocyte NeHepLxHT cell line. Similarly, tumor samples showed higher expression of APE1 in ER stress-correlated liver cancer tissue in vivo. Our results demonstrate that ER stress and HBV pre-S2∆ increased APE1 expression, which may play an important role in resistance to chemotherapeutic agents or tumor development. Therefore, these data provide an important chemotherapeutic strategy in ER stress and HBV pre-S2∆-associated tumors. View Full-Text
Keywords: hepatocellular carcinoma; Huh-7; HepG2; NeHepLxHT; hepatitis B virus; hepatitis B virus pre-S2∆ large mutant surface protein; endoplasmic reticulum stress; apurinic endonuclease 1; GRP78 hepatocellular carcinoma; Huh-7; HepG2; NeHepLxHT; hepatitis B virus; hepatitis B virus pre-S2∆ large mutant surface protein; endoplasmic reticulum stress; apurinic endonuclease 1; GRP78
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Cheng, T.-L.; Chen, P.-S.; Li, R.-H.; Yuan, S.-S.; Su, I.-J.; Hung, J.-H. Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells. Int. J. Mol. Sci. 2014, 15, 12442-12457.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top