The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies

Cancer Sci. 2003 Jan;94(1):9-14. doi: 10.1111/j.1349-7006.2003.tb01344.x.


In our laboratories, we have been studying molecular targets which might be advantageous for novel cancer therapeutics. In this review, we focus on how ATP-binding cassette (ABC) transporter superfamily genes, Y-box-binding protein-1 (YB-1), and tumor angiogenesis-associated factors could contribute to the development of novel strategies for molecular cancer therapeutics. ABC transporters such as P-glycoprotein/MDR1 and several MRP family proteins function to protect cells from xenobiotics, drugs and poisons, suggesting that ABC transporters are a double-edged sword. In this regard, P-glycoprotein/MDR1 is a representative ABC transporter which plays a critical role in the efflux of a wide range of drugs. We have reported that gene amplification, gene rearrangements, transcription factor YB-1 and CpG methylation on the promoter are involved in MDR1 gene overexpression in cultured cancer cells. Among them, two mechanisms appear to be relevant to the up-regulation of MDR1 gene in human malignancies. We first reported that MDR1 gene promoter is activated in response to environmental stimuli, and is modulated by methylation/demethylation of CpG sites on the MDR1 promoter. We also demonstrated that YB-1 modulates not only transcription of various genes associated with cell growth, drug resistance and DNA synthesis, but also translation, mRNA stabilization and DNA repair/self-defense processes. Angiogenesis is also involved in tumor growth, invasion and metastasis of various malignancies, and so angiogenesis-related molecules also offer novel molecular targets for anticancer therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • ATP-Binding Cassette Transporters / physiology*
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biological Transport
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • CpG Islands
  • DNA Methylation
  • DNA-Binding Proteins*
  • Drug Design
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Neoplasm / genetics
  • Endothelial Growth Factors / physiology*
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Genes, MDR
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Lymphokines / physiology*
  • NFI Transcription Factors
  • Neoplasm Proteins / physiology*
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / physiopathology
  • Nuclear Proteins
  • Promoter Regions, Genetic / genetics
  • Transcription Factors*
  • Transcription, Genetic
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Y-Box-Binding Protein 1


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • NFI Transcription Factors
  • Neoplasm Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Y-Box-Binding Protein 1
  • YBX1 protein, human