title: Role of Nrf2 in cancer photodynamic therapy: regulation of human ABC transporter ABCG2.
abstract: Photodynamic therapy (PDT) is a recently developed anticancer treatment that utilizes the generation of singlet oxygen and other reactive oxygen species in cancer tissue. In response to oxidative stress, NF-E2-related transcription factor (Nrf2) encoded by the NFE2L2 gene plays a key role in transcriptional upregulation of many target genes, including those for metabolizing enzymes and transporters essential for cellular defense. Recent studies have provided evidence that Nrf2 regulates the transcription of the human ABC transporter ABCG2 gene, which is critically involved in the cellular accumulation of porphyrins in PDT. Nrf2 interacts with the antioxidant responsive element (ARE) located in the promoter region of human ABCG2 gene. Nrf2-specific siRNA treatments suppressed the induction of ABCG2 expression after the photoactivation of porphyrins in vitro. One SNP (-617C>A; rs6721961) in the ARE-like loci of the human Nrf2 gene is considered to affect the positive feedback loop of transcriptional activation of the Nrf2 gene as well as its target genes including ABCG2. Since patients have demonstrated individual differences in their response to PDT, Nrf2-mediated transcriptional activation of the ABCG2 gene in cancer may affect patients' responses to PDT as well as chemotherapy.
authors: RIKEN Center for Life Science Technologies, Tsurumi-ku, Yokohama 230-0045, Japan. toshihisa.ishikawa.r@gmail.com
authors: Toshihisa
authors: T
authors: Ishikawa
authors: Yoshinaga
authors: Y
authors: Kajimoto
authors: Wei
authors: W
authors: Sun
authors: Hiroshi
authors: H
authors: Nakagawa
authors: Yutaka
authors: Y
authors: Inoue
authors: Yoji
authors: Y
authors: Ikegami
authors: Shin-Ichi
authors: S
authors: Miyatake
authors: Toshihiko
authors: T
authors: Kuroiwa
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010778:Photochemotherapy; D020641:Polymorphism, Single Nucleotide; D011166:Porphyrins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; D011166:Porphyrins; D017382:Reactive Oxygen Species
keywords: ABC transporters; Nrf2; aminolevulinic acid (ALA); cancer; gefitinib; mRNA; metabolism; oxidative stress; porphyrin; single nucleotide polymorphism (SNP)