Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells
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) express...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2014-07-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | http://www.mdpi.com/1422-0067/15/7/12442 |
id |
doaj-381acbd613f347afb1194345947e5df9 |
---|---|
record_format |
Article |
spelling |
doaj-381acbd613f347afb1194345947e5df92020-11-25T00:46:31ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-07-01157124421245710.3390/ijms150712442ijms150712442Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma CellsTsung-Lin Cheng0Pin-Shern Chen1Ren-Hao Li2Shyng-Shiou Yuan3Ih-Jen Su4Jui-Hsiang Hung5Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 71710, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 71710, TaiwanTranslational Research Center, Cancer Center, Department of Medical Research, and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70456, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 71710, TaiwanHepatocellular 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.http://www.mdpi.com/1422-0067/15/7/12442hepatocellular carcinomaHuh-7HepG2NeHepLxHThepatitis B virushepatitis B virus pre-S2∆ large mutant surface proteinendoplasmic reticulum stressapurinic endonuclease 1GRP78 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tsung-Lin Cheng Pin-Shern Chen Ren-Hao Li Shyng-Shiou Yuan Ih-Jen Su Jui-Hsiang Hung |
spellingShingle |
Tsung-Lin Cheng Pin-Shern Chen Ren-Hao Li Shyng-Shiou Yuan Ih-Jen Su Jui-Hsiang Hung Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells International Journal of Molecular Sciences 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 |
author_facet |
Tsung-Lin Cheng Pin-Shern Chen Ren-Hao Li Shyng-Shiou Yuan Ih-Jen Su Jui-Hsiang Hung |
author_sort |
Tsung-Lin Cheng |
title |
Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells |
title_short |
Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells |
title_full |
Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells |
title_fullStr |
Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells |
title_full_unstemmed |
Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells |
title_sort |
induction of apurinic endonuclease 1 overexpression by endoplasmic reticulum stress in hepatoma cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2014-07-01 |
description |
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. |
topic |
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 |
url |
http://www.mdpi.com/1422-0067/15/7/12442 |
work_keys_str_mv |
AT tsunglincheng inductionofapurinicendonuclease1overexpressionbyendoplasmicreticulumstressinhepatomacells AT pinshernchen inductionofapurinicendonuclease1overexpressionbyendoplasmicreticulumstressinhepatomacells AT renhaoli inductionofapurinicendonuclease1overexpressionbyendoplasmicreticulumstressinhepatomacells AT shyngshiouyuan inductionofapurinicendonuclease1overexpressionbyendoplasmicreticulumstressinhepatomacells AT ihjensu inductionofapurinicendonuclease1overexpressionbyendoplasmicreticulumstressinhepatomacells AT juihsianghung inductionofapurinicendonuclease1overexpressionbyendoplasmicreticulumstressinhepatomacells |
_version_ |
1725264866581676032 |