[YB-1 as a potential target in cancer therapy].
The 42-kDa multifunctional cellular protein Y-box protein 1 (YB-1) is expressed in various cancers. It is localized in the cytoplasm as well as in the nucleus. In particular, YB-1 is localized in the nuclear compartment following cellular stress, such as radiation, drug treatment, hyperthermia, or viral infection. Within the nucleus, YB-1 can act as a transcription factor, and it is involved in the regulation of important cancer-associated genes. For example, YB-1 triggers the expression of Her-2 and estrogen receptor alpha (ERalpha) in breast cancer. Thus, nuclear YB-1 appears to be a potential target for the inhibition of Her-2- and ERalpha-dependent proliferation signals, particularly with regard to resistance to Her-2-targeting drugs such as trastuzumab. In some cancers, YB-1 may be involved in regulating MDR1/P-glycoprotein, mediating classical multidrug resistance (MDR). Furthermore, YB-1 is involved in the replication of adenovirus type 5, a commonly used vector in gene therapy. Thus, YB-1 can trigger an "oncolytic" effect in YB-1 nuclear positive cancer cells treated with adenoviruses. Besides its impact as a prognostic factor, in the future the diagnostics of cellular YB-1 status may provide the basis for a virotherapy or a gene therapy incorporating adenoviruses.
Lage
H
H
Institut für Pathologie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin. hermann.lage@charite.de
Surowiak
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P
Holm
P S
PS
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D009687:Nuclear Proteins / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D051840:Y-Box-Binding Protein 1
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D051840:Y-Box-Binding Protein 1; C513055:ABCB1 protein, human; C070856:YBX1 protein, human; C508053:ERBB2 protein, human
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