Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression

Nat Med. 1997 Apr;3(4):447-50. doi: 10.1038/nm0497-447.


Breast cancers are either primarily resistant to chemotherapy (intrinsic resistance), or respond to chemotherapy but later recur with a multidrug-resistant phenotype because of overexpression of the multidrug transporter P-glycoprotein. The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-box transcription factor. We now report that, in multidrug-resistant MCF-7 breast cancer cells, nuclear localization of YB-1 is associated with MDR-1 gene expression. In drug-sensitive MCF-7 cells, however, YB-1 was localized to the cytoplasm. Regulated overexpression of YB-1 in drug-sensitive diploid breast epithelial cells induced MDR-1 gene expression and multidrug resistance. In 27 out of 27 untreated primary breast cancers, YB-1 protein was expressed in the cytoplasm although it was undetectable in normal breast tissue of these patients. In a subgroup of tumors (9/27), however, YB-1 was also localized to the nucleus and, in these cases, high levels of P-glycoprotein were present. These results show that in a subset of untreated primary breast cancers, nuclear localization of YB-1 protein is associated with intrinsic multidrug resistance. Our data show that YB-1 has an important role in controlling MDR1 gene transcription and this finding provides a basis for the analysis of molecular mechanisms responsible for intrinsic multidrug resistance in human breast cancer.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adult
  • Aged
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • CCAAT-Enhancer-Binding Proteins*
  • Cell Compartmentation
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / metabolism*
  • Drug Resistance, Multiple / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • NFI Transcription Factors
  • Nuclear Proteins
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Y-Box-Binding Protein 1


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • NFI Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • Y-Box-Binding Protein 1
  • YBX1 protein, human