AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells

Oncogene. 2006 Aug 31;25(39):5405-15. doi: 10.1038/sj.onc.1209534. Epub 2006 Apr 24.


Activating enhancer-binding protein 2alpha (AP-2alpha) and activating enhancer-binding protein 2gamma (AP-2gamma) are transcription factors that bind GC-rich consensus sequences and regulate the expression of many downstream genes. AP-2alpha and AP-2gamma interact with p53 both physically and functionally. Expression microarray results in human breast carcinoma cells with forced p53 expression revealed AP-2gamma as a putative transcriptional target of p53. To confirm and extend these findings we measured the effects of forced p53 expression in human breast carcinoma cells by real-time reverse transcription-PCR, Western blotting, electrophoretic gel mobility shift assays, promoter reporter, chromatin immunoprecipitation and chromatin accessibility assays. Wild-type p53 expression rapidly induced not only AP-2gamma but also AP-2alpha mRNA. The subsequent increase in these proteins led to increased AP-2 DNA-binding and transactivating activity. Candidate p53-binding sites were identified in the AP-2alpha and AP-2gamma promoters. p53 binding to these cis-elements in vivo was also observed, together with a relaxation of chromatin structure in these regions. Finally, expression of either AP-2alpha or gamma inhibited growth of human breast carcinoma cells in vitro. Taken together, our findings indicate that these AP-2 genes are targets for transcriptional activation by p53 and suggest that AP-2 proteins may mediate some of the downstream effects of p53 expression such as inhibition of proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Breast Neoplasms / genetics
  • Cell Division
  • Cell Line, Tumor
  • DNA Primers
  • Female
  • Genes, Reporter
  • Genes, p53*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Plasmids
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor AP-2 / genetics*
  • Transcription Factor AP-2 / metabolism
  • Transcription, Genetic
  • Transfection


  • DNA Primers
  • Transcription Factor AP-2