Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy.

Molecular Cancer
Adam ListerB Kevin Park

Abstract

Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer. Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of NRF2 exon 2 and KEAP1 exons 2-6 in these cell lines identified no mutations in NRF2 and only synonomous mutations in KEAP1. RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestin...Continue Reading

References

Jan 15, 2002·Virchows Archiv : an International Journal of Pathology·P S MooreA Scarpa
Sep 18, 2002·The Journal of Biological Chemistry·Hiromi SasakiShiro Bannai
Mar 19, 2004·The New England Journal of Medicine·John P NeoptolemosUNKNOWN European Study Group for Pancreatic Cancer
Jan 20, 2005·Molecular and Cellular Biology·Ruben N KarapetianAndrey B Vartapetian
Feb 3, 2005·International Journal of Cancer. Journal International Du Cancer·Jörg KönigDietrich Keppler
May 18, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pascal O BerberatHelmut Friess
Jun 8, 2006·Journal of Biochemistry and Molecular Biology·Wen LinAh-Ng Tony Kong
Aug 5, 2006·Advances in Enzyme Regulation·Makoto Kobayashi, Masayuki Yamamoto
Nov 4, 2006·Biological Chemistry·Kit I TongMasayuki Yamamoto
Apr 25, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Malcolm J MooreUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Aug 3, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jonathan M MaherCurtis D Klaassen
Dec 20, 2007·Applied Immunohistochemistry & Molecular Morphology : AIMM·Nida S AwadallahKenneth R Shroyer
Feb 2, 2008·The Journal of Biological Chemistry·Melanie TheodoreIfeanyi J Arinze
Jun 17, 2008·Biochemical and Biophysical Research Communications·Rui WangDeshan Zhou
Jul 12, 2008·Molecular Carcinogenesis·Wenge Li, Ah-Ng Kong
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tatsuhiro ShibataSetsuo Hirohashi
Sep 12, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ian M CoppleB Kevin Park
Nov 26, 2008·Cancer Treatment Reviews·Ghassan El MaaloufEric Raymond
Mar 27, 2009·Trends in Biochemical Sciences·John D Hayes, Michael McMahon
May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shinsuke HommaMasayuki Yamamoto
May 29, 2009·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Jun 11, 2009·Molecular Cancer·Philipp NuhnPascal O Berberat
Jun 16, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Hanane AkhdarFabrice Morel
Oct 28, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David CunninghamJohn P Neoptolemos
Jan 27, 2010·Nature Reviews. Clinical Oncology·Anastasios Stathis, Malcolm J Moore
Apr 10, 2010·The Journal of Biological Chemistry·Ian M CoppleB Kevin Park

❮ Previous
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Citations

Sep 20, 2011·The Journal of Biological Chemistry·Gabriel EadesQun Zhou
Mar 22, 2014·PloS One·Barbara A HocevarE Gabriela Chiorean
Dec 25, 2013·International Journal of Oncology·Hong-Quan DuongInsoo Bae
Jul 18, 2014·Virchows Archiv : an International Journal of Pathology·Makoto SanoNorimichi Nemoto
Oct 22, 2013·Genes & Development·Melba C Jaramillo, Donna D Zhang
Oct 16, 2013·Critical Reviews in Oncology/hematology·Suna ZhouJun Liang
Oct 27, 2015·The Journal of Pathology·Wafa Abu-AlaininEithne Costello
Sep 10, 2015·Pathology Oncology Research : POR·Cong-Fa HuangZhi-Jun Sun
Jan 16, 2016·Oxidative Medicine and Cellular Longevity·Hilal S KhalilYusuf Y Deeni
Oct 1, 2015·The Journal of Nutritional Biochemistry·Ying HuangAh-Ng Tony Kong
Jan 1, 2014·International Journal of Cancer. Journal International Du Cancer·Xiangjun JiSuihua Chen
Mar 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Papavee SamatiwatVeerapol Kukongviriyapan
Aug 12, 2014·Biochemical Society Transactions·David J MacEwanLyubov Zaitseva
May 31, 2014·The International Journal of Biochemistry & Cell Biology·Lin Li, Po Sing Leung
Apr 7, 2015·Molecular Oncology·Monique G P van der WijstMarianne G Rots
Jun 29, 2015·The International Journal of Biochemistry & Cell Biology·Alastair J HayesRichard M Charnley
Apr 9, 2015·BMC Cancer·Sangeetha Sukumari-RameshKrishnan M Dhandapani
Feb 25, 2015·Naunyn-Schmiedeberg's Archives of Pharmacology·Papavee SamatiwatVeerapol Kukongviriyapan
Oct 2, 2014·Biochimica Et Biophysica Acta·Monique G P van der WijstMarianne G Rots
Aug 6, 2011·Free Radical Biology & Medicine·Piergiorgio PettazzoniGiuseppina Barrera
Apr 16, 2013·Genomics, Proteomics & Bioinformatics·Lei YangSiqi Liu
Dec 12, 2012·Biochemical Pharmacology·Holly K BryanB Kevin Park
May 20, 2014·Urologic Oncology·Annette HaydenSimon J Crabb
Jun 28, 2016·International Journal of Molecular Sciences·Xiaohui SunQiang Liu
Apr 20, 2014·Carcinogenesis·Cristovão Marques Sousa, Alec C Kimmelman

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Methods Mentioned

BETA
transfection
surgical resection
PCR
Genotyping

Software Mentioned

BLAST
GeneMapper
Statview

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