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

doi:10.3390/ijms150712442

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標題:	Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells
作者:	Cheng, Tsung-Lin Chen, Pin-Shern Li, Ren-Hao Yuan, Shyng-Shiou Su, Ih-Jen Hung, Jui-Hsiang
貢獻者:	生物科技系新藥創建研究中心
關鍵字:	hepatocellular carcinoma Huh-7 HepG2 NeHepLxHT hepatitis B virus hepatitis B virus pre-S2 Delta large mutant surface protein endoplasmic reticulum stress apurinic endonuclease 1 GRP78
日期:	2014-07
上傳時間:	2015-05-06 21:22:11 (UTC+8)
出版者:	Mdpi Ag
摘要:	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 Delta large mutant surface protein (pre-S2 Delta), 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 Delta 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 Delta-associated tumors.
關聯:	International Journal of Molecular Sciences, v.15 n.7, pp.12442-12457
显示于类别:	[生物科技系(所)] 期刊論文

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