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.
Begon
Dominique Y
DY
Molecular Oncology Laboratory, Centre of Biomedical Integrative Genoproteomics, Experimental Cancer Research Centre, University of Liege, Sart-Tilman, 4000 Liege, Belgium.
Delacroix
Laurence
L
Vernimmen
Douglas
D
Jackers
Pascale
P
Winkler
Rosita
R
D001665:Binding Sites; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D050981:Erythroid-Specific DNA-Binding Factors; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D008957:Models, Genetic; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D050986:YY1 Transcription Factor
D002843:Chromatin; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D008156:Luciferases; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C493673:TFAP2A protein, human; C494698:YY1 protein, human