title: Oct-3/4 modulates the drug-resistant phenotype of glioblastoma cells through expression of ATP binding cassette transporter G2.
abstract: BACKGROUND
  Drug resistance is a major obstacle for the efficacy of chemotherapeutic treatment of tumors. Oct-3/4, a self-renewal regulator in stem cells, is expressed in various kinds of solid tumors including glioblastoma. Although Oct-3/4 expression has been implicated in the malignancy and prognosis of glioblastomas, little is known of its involvement in drug resistances of glioblastoma.
  
  
  METHODS
  The involvement of Oct-3/4 in drug resistance of glioblastoma cells was assessed by lactate dehydrogenase assay, efflux assay of an anticancer drug, poly ADP-ribose polymerase cleavage, and in vivo xenograft experiments. Involvement of a drug efflux pump ATP binding cassette transporter G2 in Oct-3/4-induced drug resistance was evaluated by quantitative PCR analysis and knockdown by shRNA.
  
  
  RESULTS
  Oct-3/4 decreased the susceptibility to chemotherapeutic drugs by enhancing excretion of drugs through a drug efflux pump gene, ATP binding cassette transporter G2. Moreover, the expression of Oct-3/4 was well correlated to ATP binding cassette transporter G2 expression in clinical GB tissues.
  
  
  CONCLUSIONS
  Oct-3/4 elevated the ATP binding cassette transporter G2 expression, leading to acquisition of a drug-resistant phenotype by glioblastoma cells.
  
  
  CONCLUSIONS
  If the drug-resistance of glioblastoma cells could be suppressed, it should be a highly ameliorative treatment for glioblastoma patients. Therefore, signaling pathways from Oct-3/4 to ATP binding cassette transporter G2 should be intensively elucidated to develop new therapeutic interventions for better efficacy of anti-cancer drugs.
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Yuki
authors: Y
authors: Hosokawa
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan. Electronic address: hisaaki@m.ehime-u.ac.jp.
authors: Hisaaki
authors: H
authors: Takahashi
authors: Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Akihiro
authors: A
authors: Inoue
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Yuya
authors: Y
authors: Kawabe
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Yu
authors: Y
authors: Funahashi
authors: Integrated Center for Science, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Kenji
authors: K
authors: Kameda
authors: Department of Legal Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors: Kana
authors: K
authors: Sugimoto
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Hajime
authors: H
authors: Yano
authors: Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Hironobu
authors: H
authors: Harada
authors: Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Shohei
authors: S
authors: Kohno
authors: Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Shiro
authors: S
authors: Ohue
authors: Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Takanori
authors: T
authors: Ohnishi
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Junya
authors: J
authors: Tanaka
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases
keywords: ABC transporter; Drug resistance; Glioblastoma; Oct-3/4