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 language | English (US) |
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Pages (from-to) | 209-220 |
Number of pages | 12 |
Journal | Journal of Cellular Biochemistry |
Volume | 99 |
Issue number | 1 |
DOIs | |
State | Published - Sep 1 2006 |
Keywords
- Activation
- Breast cancer
- Estrogen
- cdc25A
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology