1. 17β-estradiol (E2) induces cdc25A gene expression in breast cancer cells by genomic and non-genomic pathways
- Author
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Shengxi Liu, Stephen Safe, Wan Ru Lee, and Chien-Cheng Chen
- Subjects
CDC25A ,Sp1 Transcription Factor ,Breast Neoplasms ,Protein tyrosine phosphatase ,Xenopus Proteins ,Biology ,Response Elements ,medicine.disease_cause ,Retinoblastoma Protein ,Biochemistry ,Cyclin-dependent kinase ,Gene expression ,Cyclic AMP ,Tumor Cells, Cultured ,medicine ,Humans ,cdc25 Phosphatases ,Promoter Regions, Genetic ,E2F ,Molecular Biology ,Cyclin ,Base Composition ,Mutation ,Binding Sites ,Estradiol ,Kinase ,Estrogen Receptor alpha ,Cell Biology ,Cyclic AMP-Dependent Protein Kinases ,Molecular biology ,E2F Transcription Factors ,Gene Expression Regulation, Neoplastic ,CCAAT-Binding Factor ,Transcription Factor TFIIB ,biology.protein ,Female ,E2F1 Transcription Factor ,Signal Transduction ,Transcription Factors - 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. J. Cell. Biochem. © 2006 Wiley-Liss, Inc.
- Published
- 2006