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Title: Role of hypoxia-inducible factor-{alpha} in hepatitis-B-virus X protein-mediated MDR1 activation

Abstract

The transition from chemotherapy-responsive cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multi-drug resistance 1 (MDR1). We found that hepatitis-B-virus X protein (HBx) increases the transcriptional activity and protein level of MDR1 in a hepatoma cell line, H4IIE. In addition, HBx overexpression made H4IIE cells more resistant to verapamil-uptake. HBx stabilized hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and induced the nuclear translocation of C/EBP{beta}. Reporter gene analyses showed that HBx increased the reporter activity in the cells transfected with the reporter containing MDR1 gene promoter. Moreover, the luciferase reporter gene activity was significantly inhibited by HIF-1{alpha} siRNA but not by overexpression of C/EBP dominant negative mutant. These results imply that HBx increases the MDR1 transporter activity through the transcriptional activation of the MDR1 gene with HIF-1{alpha} activation, and suggest HIF-1{alpha} for the therapeutic target of HBV-mediated chemoresistance.

Authors:
 [1];  [1];  [1];  [2];  [3]
  1. BK21 Project Team, College of Pharmacy, Chosun University, Gwangju 501-759, South Korea (Korea, Republic of)
  2. College of Pharmacy, Pusan National University, Busan 609-735, South Korea (Korea, Republic of)
  3. BK21 Project Team, College of Pharmacy, Chosun University, Gwangju 501-759, South Korea (Korea, Republic of). E-mail: kwkang@chosun.ac.kr
Publication Date:
OSTI Identifier:
20991371
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 357; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2007.04.012; PII: S0006-291X(07)00725-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANOXIA; CHEMOTHERAPY; DRUGS; GENES; HEPATITIS; HEPATOMAS; LUCIFERASE; MUTANTS; PROMOTERS; TRANSLOCATION; VIRUSES

Citation Formats

Han, Hyo-Kyung, Han, Chang Yeob, Cheon, Eun-Pa, Lee, Jaewon, and Kang, Keon Wook. Role of hypoxia-inducible factor-{alpha} in hepatitis-B-virus X protein-mediated MDR1 activation. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.04.012.
Han, Hyo-Kyung, Han, Chang Yeob, Cheon, Eun-Pa, Lee, Jaewon, & Kang, Keon Wook. Role of hypoxia-inducible factor-{alpha} in hepatitis-B-virus X protein-mediated MDR1 activation. United States. doi:10.1016/j.bbrc.2007.04.012.
Han, Hyo-Kyung, Han, Chang Yeob, Cheon, Eun-Pa, Lee, Jaewon, and Kang, Keon Wook. Fri . "Role of hypoxia-inducible factor-{alpha} in hepatitis-B-virus X protein-mediated MDR1 activation". United States. doi:10.1016/j.bbrc.2007.04.012.
@article{osti_20991371,
title = {Role of hypoxia-inducible factor-{alpha} in hepatitis-B-virus X protein-mediated MDR1 activation},
author = {Han, Hyo-Kyung and Han, Chang Yeob and Cheon, Eun-Pa and Lee, Jaewon and Kang, Keon Wook},
abstractNote = {The transition from chemotherapy-responsive cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multi-drug resistance 1 (MDR1). We found that hepatitis-B-virus X protein (HBx) increases the transcriptional activity and protein level of MDR1 in a hepatoma cell line, H4IIE. In addition, HBx overexpression made H4IIE cells more resistant to verapamil-uptake. HBx stabilized hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and induced the nuclear translocation of C/EBP{beta}. Reporter gene analyses showed that HBx increased the reporter activity in the cells transfected with the reporter containing MDR1 gene promoter. Moreover, the luciferase reporter gene activity was significantly inhibited by HIF-1{alpha} siRNA but not by overexpression of C/EBP dominant negative mutant. These results imply that HBx increases the MDR1 transporter activity through the transcriptional activation of the MDR1 gene with HIF-1{alpha} activation, and suggest HIF-1{alpha} for the therapeutic target of HBV-mediated chemoresistance.},
doi = {10.1016/j.bbrc.2007.04.012},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 357,
place = {United States},
year = {Fri Jun 01 00:00:00 EDT 2007},
month = {Fri Jun 01 00:00:00 EDT 2007}
}