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Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mammary cancer cells.

Overexpression of the ERBB2 oncogene is observed in about 30% of breast cancers and is generally correlated with a poor prognosis. Previous results from our and other laboratories indicated that elevated transcriptional activity contributes significantly to the overexpression of ERBB2 mRNA in mammary adenocarcinoma cell lines. Activator protein 2 (AP-2) transcription factors account for this overexpression through two recognition sequences located 215 and 500 bp upstream from the transcription start site. Furthermore, AP-2 transcription factors are highly expressed in cancer cell lines overexpressing ERBB2. In this report, we examined the cooperative effect of Yin Yang 1 (YY1) on AP-2-induced activation of ERBB2 promoter activity. We detected high levels of YY1 transcription factor in mammary cancer cell lines. Notably, we showed that YY1 enhances AP-2alpha transcriptional activation of the ERBB2 promoter through an AP-2 site both in HepG2 and in HCT116 cells, whereas a carboxyl-terminal-truncated form of YY1 cannot. Moreover, we demonstrated the interaction between endogenous AP-2 and YY1 factors in the BT-474 mammary adenocarcinoma cell line. In addition, inhibition of endogenous YY1 protein by an antisense decreased the transcription of an AP-2-responsive ERBB2 reporter plasmid in BT-474 breast cancer cells. Finally, we detected in vivo AP-2 and YY1 occupancy of the ERBB2 proximal promoter in chromatin immunoprecipitation assays. Our data thus provide evidence that YY1 cooperates with AP-2 to stimulate ERBB2 promoter activity through the AP-2 binding sites.

Pubmed ID: 15870067

Authors

  • Begon DY
  • Delacroix L
  • Vernimmen D
  • Jackers P
  • Winkler R

Journal

The Journal of biological chemistry

Publication Data

July 1, 2005

Associated Grants

None

Mesh Terms

  • Binding Sites
  • Blotting, Western
  • Breast Neoplasms
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus
  • Chromatin
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • Gene Expression Regulation, Neoplastic
  • Genetic Vectors
  • Humans
  • Immunoprecipitation
  • Luciferases
  • Models, Genetic
  • Oligonucleotides, Antisense
  • Plasmids
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Messenger
  • Receptor, ErbB-2
  • Transcription Factor AP-2
  • Transcription Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection
  • YY1 Transcription Factor