TY - JOUR
T1 - Transcriptional activation of cathepsin D gene expression by 17β-estradiol
T2 - Mechanism of aryl hydrocarbon receptor-mediated inhibition
AU - Wang, Fan
AU - Samudio, Ismael
AU - Safe, Stephen
PY - 2001/2/14
Y1 - 2001/2/14
N2 - 17β-estradiol (E2) induces cathepsin D gene expression in MCF-7 human breast cancer cells and this response is inhibited by aryl hydrocarbon receptor (AhR) agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Analysis of the cathepsin D gene promoter initially identified a pentanucleotide GCGTG core dioxin responsive element (DRE) that blocked E2 action by inhibiting formation of a transcriptionally active estrogen receptor (ER)-Sp1 complex. A second functional downstream inhibitory DRE (iDRE2) (-130 to -126) has now been identified in the cathepsin D gene promoter and inhibition of E2-induced transactivation involves inhibitory AhR crosstalk with the E2-responsive adenovirus major late promoter element (MLPE) at -124 to -104 in the cathepsin D gene promoter. The MLPE site primarily binds USF1/USF2 and ERα, and gel mobility shift and DNA footprinting assays show that the AhR complex decreases binding of these transcription factors to the MLPE.
AB - 17β-estradiol (E2) induces cathepsin D gene expression in MCF-7 human breast cancer cells and this response is inhibited by aryl hydrocarbon receptor (AhR) agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Analysis of the cathepsin D gene promoter initially identified a pentanucleotide GCGTG core dioxin responsive element (DRE) that blocked E2 action by inhibiting formation of a transcriptionally active estrogen receptor (ER)-Sp1 complex. A second functional downstream inhibitory DRE (iDRE2) (-130 to -126) has now been identified in the cathepsin D gene promoter and inhibition of E2-induced transactivation involves inhibitory AhR crosstalk with the E2-responsive adenovirus major late promoter element (MLPE) at -124 to -104 in the cathepsin D gene promoter. The MLPE site primarily binds USF1/USF2 and ERα, and gel mobility shift and DNA footprinting assays show that the AhR complex decreases binding of these transcription factors to the MLPE.
KW - Ah receptor
KW - Cathepsin D
KW - ER
KW - Inhibitory crosstalk
UR - http://www.scopus.com/inward/record.url?scp=0035857478&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035857478&partnerID=8YFLogxK
U2 - 10.1016/S0303-7207(00)00379-8
DO - 10.1016/S0303-7207(00)00379-8
M3 - Article
C2 - 11165043
AN - SCOPUS:0035857478
VL - 172
SP - 91
EP - 103
JO - Molecular and cellular endocrinology
JF - Molecular and cellular endocrinology
SN - 0303-7207
IS - 1-2
ER -