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

Authors
Young Bin HongHyo Jin KangSun Young KwonHee Jeong KimKun Young KwonChi Heum ChoJong-Min LeeBhaskar V.S. KallakuryInsoo Bae
Department
Dept. of Pathology (병리학); Dept. of Obstetrics & Gynecology (산부인과학)
Issue Date
2010
Citation
Pancreas, Vol.39(4) : 463-472, 2010
ISSN
0885-3177
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
Keywords
Nrf2drug resistancepancreatic cancer
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/33635
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
Keimyung Author(s)
권선영; 권건영; 조치흠
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