[YB-1 as a potential target in cancer therapy]

Pathologe. 2008 Nov;29 Suppl 2:187-90. doi: 10.1007/s00292-008-1030-2.
[Article in German]

Abstract

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.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adenoviruses, Human / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy
  • Cell Division / genetics
  • DNA-Binding Proteins / genetics*
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Neoplasm / genetics
  • Estrogen Receptor alpha / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Targeting*
  • Gene Transfer Techniques*
  • Genetic Therapy*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / therapy*
  • Nuclear Proteins / genetics*
  • Receptor, ErbB-2 / genetics
  • Y-Box-Binding Protein 1

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • DNA-Binding Proteins
  • Estrogen Receptor alpha
  • Nuclear Proteins
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2