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

Wan Ru Lee, Chien Cheng Chen, Shengxi Liu, Stephen Safe

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 17β-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 ERα/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.

Original languageEnglish (US)
Pages (from-to)209-220
Number of pages12
JournalJournal of Cellular Biochemistry
Volume99
Issue number1
DOIs
StatePublished - Sep 1 2006

Keywords

  • Activation
  • Breast cancer
  • cdc25A
  • Estrogen

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of '17β-estradiol (E2) induces cdc25A gene expression in breast cancer cells by genomic and non-genomic pathways'. Together they form a unique fingerprint.

Cite this