title: Cisplatin resistance and transcription factors.
abstract: Cisplatin is one of the most potent and widely used anti-cancer agents in the treatment of various solid tumors. However, the development of resistance to cisplatin is a major obstacle in clinical treatment. Several mechanisms are thought to be involved in cisplatin resistance, including decreased intracellular drug accumulation, increased levels of cellular thiols, increased nucleotide excision-repair activity and decreased mismatch-repair activity. In general, the molecules responsible for each mechanism are upregulated in cisplatin-resistant cells; this indicates that the transcription factors activated in response to cisplatin might play crucial roles in drug resistance. It is known that the tumor-suppressor proteins p53 and p73, and the oncoprotein c-Myc, which function as transcription factors, influence cellular sensitivity to cisplatin. So far, we have identified several transcription factors involved in cisplatin resistance, including Y-box binding protein-1 (YB-1), CCAAT-binding transcription factor 2 (CTF2), activating transcription factor 4 (ATF4), zinc-finger factor 143 (ZNF143) and mitochondrial transcription factor A (mtTFA). Two of these-YB-1 and ZNF143-lack the high-mobility group (HMG) domain and can bind preferentially to cisplatin-modified DNA in addition to HMG domain proteins or DNA repair proteins, indicating that these transcription factors may also participate in DNA repair. In this review, we summarize the mechanisms of cisplatin resistance and focus on transcription factors involved in the genomic response to cisplatin.
authors.affiliation: Department of Molecular Biology, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Torigoe
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishiguchi
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Mizuho
authors.initials: M
authors.lastname: Tanabe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tomonori
authors.initials: T
authors.lastname: Igarashi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Niina
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Wakasugi
authors.forename: Takuya
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Momii
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
mesh_terms: D051701:Activating Transcription Factor 4; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D023081:CCAAT-Binding Factor / Q000502:physiology; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D002945:Cisplatin / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006609:High Mobility Group Proteins / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051839:NFI Transcription Factors; D009687:Nuclear Proteins / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins; D051840:Y-Box-Binding Protein 1
chemical_list: C497109:ATF4 protein, human; D023081:CCAAT-Binding Factor; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C116115:MYCBP protein, human; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051840:Y-Box-Binding Protein 1; C114253:ZNF143 protein, human; D051701:Activating Transcription Factor 4; D002945:Cisplatin