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

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.

published proceedings

  • J Cell Biochem

author list (cited authors)

  • Ru Lee, W., Chen, C., Liu, S., & Safe, S.

citation count

  • 17

complete list of authors

  • Ru Lee, Wan||Chen, Chien-Cheng||Liu, Shengxi||Safe, Stephen

publication date

  • September 2006

publisher