17beta-estradiol (E2) induces cdc25A gene expression in breast cancer cells by genomic and non-genomic pathways

J Cell Biochem. 2006 Sep 1;99(1):209-20. doi: 10.1002/jcb.20902.

Abstract

Cdc25A is a potent tyrosine phosphatase that catalyzes specific dephosphorylation of cyclin/cyclin-dependent kinase (cdk) complexes to regulate G1 to S-phase cell cycle progression. Cdc25A mRNA levels are induced by 17beta-estradiol (E2) in ZR-75 breast cancer cells, and deletion analysis of the cdc25A promoter identified the -151 to -12 region as the minimal E2-responsive sequence. Subsequent mutation/deletion analysis showed that at least three different cis-elements were involved in activation of cdc25A by E2, namely, GC-rich Sp1 binding sites, CCAAT motifs that bind NF-Y, and E2F sites that bind DP/E2F1 proteins. Studies with inhibitors and dominant negative expression plasmids show that E2 activates cdc25A expression through activation of genomic ERalpha/Sp1 and E2F1 and cAMP-dependent activation of NF-YA. Thus, both genomic and non-genomic pathways of estrogen action are involved in induction of cdc25A in breast cancer cells.

MeSH terms

  • Base Composition
  • Binding Sites
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • CCAAT-Binding Factor / genetics
  • CCAAT-Binding Factor / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • E2F Transcription Factors / genetics
  • E2F Transcription Factors / metabolism
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism
  • Estradiol / metabolism
  • Estradiol / pharmacology*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mutation
  • Promoter Regions, Genetic
  • Response Elements
  • Retinoblastoma Protein / metabolism
  • Signal Transduction
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism
  • Transcription Factor TFIIB / genetics
  • Transcription Factor TFIIB / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • cdc25 Phosphatases / drug effects
  • cdc25 Phosphatases / genetics*
  • cdc25 Phosphatases / metabolism

Substances

  • CCAAT-Binding Factor
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Estrogen Receptor alpha
  • NFYA protein, Xenopus
  • Retinoblastoma Protein
  • Sp1 Transcription Factor
  • Transcription Factor TFIIB
  • Transcription Factors
  • Xenopus Proteins
  • nuclear factor Y
  • Estradiol
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • CDC25A protein, human
  • cdc25 Phosphatases