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Nuclear factor (erythroid-derived 2)-like 2 regulates drug resistance in pancreatic cancer cells

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Author(s)
Young Bin HongHyo Jin KangSun Young KwonHee Jeong KimKun Young KwonChi Heum ChoJong-Min LeeBhaskar V.S. KallakuryInsoo Bae
Keimyung Author(s)
Kwon, Sun YoungKwon, Kun YoungCho, Chi Heum
Department
Dept. of Pathology (병리학)
Dept. of Obstetrics & Gynecology (산부인과학)
Journal Title
Pancreas
Issued Date
2010
Volume
39
Issue
4
Keyword
Nrf2drug resistancepancreatic cancer
Abstract
Objective
To investigate the molecular basis of drug resistance in pancreatic cancer.

Methods
The expression of Nrf2 levels in pancreatic cancer tissues and cell lines was analyzed. Clinical relevance between Nrf2 activation and drug resistance was demonstrated by measuring cell viability after Nrf2 and ABCG2 regulation by over-expression or knockdown of these genes. Activity of ABCG2 was measured by Hoechst 33342 staining.

Results
Abnormally elevated Nrf2 protein levels were observed in pancreatic cancer tissues and cell lines relative to normal pancreatic tissues. Increasing Nrf2 protein levels either by over-expression of exogenous Nrf2 or by activating endogenous Nrf2 resulted in increased drug resistance. Conversely, a reduction in endogenous Nrf2 protein levels or inactivation of endogenous Nrf2 resulted in decreased drug resistance. These changes in drug resistance or sensitivity were also positively correlated to the expression levels of Nrf2 downstream genes. Similarly, the expression of ABCG2 was correlated with drug resistance.

Conclusions
Since the intrinsic drug resistance of pancreatic cancers is, in part, due to abnormally elevated Nrf2 protein levels, further research on regulating Nrf2 activity may result in the development of novel pancreatic cancer therapies.

Keywords: Nrf2, drug resistance, pancreatic cancer
Keimyung Author(s)(Kor)
권선영
권건영
조치흠
Publisher
School of Medicine
Citation
Young Bin Hong et al. (2010). Nuclear factor (erythroid-derived 2)-like 2 regulates drug resistance in pancreatic cancer cells. Pancreas, 39(4), 463–472. doi: 10.1097%2FMPA.0b013e3181c31314
Type
Article
ISSN
0885-3177
DOI
10.1097%2FMPA.0b013e3181c31314
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33635
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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