1. A Somatic Mutation of the KEAP1 Gene in Malignant Melanoma Is Involved in Aberrant NRF2 Activation and an Increase in Intrinsic Drug Resistance 
Shinpei Miura, Masahiko Shibazaki, Shuya Kasai, Shinji Yasuhira, Ayano Watanabe, Tsuyoshi Inoue, Yuich Kageshita, Kanako Tsunoda, Kazuhiro Takahashi, Toshihide Akasaka, Tomoyuki Masuda, Chihaya Maesawa 
Journal of Investigative Dermatology 
Volume 134, Issue 2, Pages (February 2014)
DOI: /jid
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2. Figure 1
NRF2 contributes to chemoresistance in KEAP1-FSM cells. (a) Representative electrophoretograms of KEAP1 gene exon 4 by capillary sequencing in melanoma cell lines. Arrowheads indicate the single-nucleotide deletion at codon 507 (1518delC). (b) Schematic representation of the KEAP1 protein. Arrowheads indicate the appearance of a stop codon. (c) Expression of NRF2 protein in siCtrl- or siNRF2-transfected PM-WK cells. (d) Quantification of the ratio of reduced-to-oxidized glutathione (GSH/GSSG) or (e) intracellular reactive oxygen species levels after treatment with vehicle, CDDP, or DTIC in siCtrl- or siNRF2-transfected PM-WK cells. (f) Cell viability at 24 hours after treatment with vehicle, CDDP, or DTIC in siCtrl- or siNRF2-transfected PM-WK cells. NS, no significant difference; *P<0.05 and **P<0.01 versus control by t-test. CDDP, cis-diamminedichloro-platinum (II); DTIC, 5-(3, 3-dimethyl-1-triazenyl) imidazole-4-carboxamide.
Journal of Investigative Dermatology  , DOI: ( /jid )
Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

3. Figure 2
Aberrant NRF2 protein accumulation in primary melanomas harboring KEAP1 frameshift mutation (FSM). Immunohistochemical analysis of endogenous NRF2 protein expression in melanomas harboring the KEAP1 FSM (a and b, # ; c and d, # ) and with wild-type KEAP1 (e and f, # ; g and h, # ). Cells were stained with NRF2 antibody. High-magnification images correspond to the respective boxed areas in the loupe images. Bar=100 μm.
Journal of Investigative Dermatology  , DOI: ( /jid )
Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions