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17β‐estradiol (E2) induces cdc25A gene expression in breast cancer cells by genomic and non‐genomic pathways
Author(s) -
Ru Lee Wan,
Chen ChienCheng,
Liu Shengxi,
Safe Stephen
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20902
Subject(s) - cdc25a , microbiology and biotechnology , e2f , biology , cancer research , cell cycle , chemistry , gene , cell cycle checkpoint , genetics
Cdc25A is a potent tyrosine phosphatase that catalyzes specific dephosphorylation of cyclin/cyclin‐dependent kinase (cdk) complexes to regulate G 1 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.