TY - JOUR
T1 - Role of specificity protein transcription factors in estrogen-induced gene expression in MCF-7 breast cancer cells
AU - Khan, Shaheen
AU - Wu, Fei
AU - Liu, Shengxi
AU - Wu, Qian
AU - Safe, Stephen
PY - 2007/9
Y1 - 2007/9
N2 - Deletion analysis of several 17β-estradiol (E2)-responsive genes have identified GC-rich sites that are associated with hormone-induced transactivation in MCF-7 breast cancer cells. However, the role of individual specificity proteins (Sps) in mediating hormone-induced gene expression has not been unequivocally determined. In transient transfection studies using E2-responsive GC-rich promoters from the E2F1, carbamoylphosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD), and retinoic acid receptor α (RARα) genes, RNA interference using small inhibitory RNAs for Sp1 (iSp1), Sp3 (iSp3), and Sp4 (iSp4) decreased both basal and E2-induced transactivation. The contributions of individual Sp proteins to basal and E2-induced activity were promoter dependent, iSp1, iSp3, and iSp4 also significantly inhibited hormonal induction of E2F1, CAD, and RARα mRNA levels; however, the enhanced inhibitory effects of the latter two small inhibitory RNAs suggest that Sp3 and Sp4 play a major role in estrogen receptor α/Sp-mediated gene expression in MCF-7 cells.
AB - Deletion analysis of several 17β-estradiol (E2)-responsive genes have identified GC-rich sites that are associated with hormone-induced transactivation in MCF-7 breast cancer cells. However, the role of individual specificity proteins (Sps) in mediating hormone-induced gene expression has not been unequivocally determined. In transient transfection studies using E2-responsive GC-rich promoters from the E2F1, carbamoylphosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD), and retinoic acid receptor α (RARα) genes, RNA interference using small inhibitory RNAs for Sp1 (iSp1), Sp3 (iSp3), and Sp4 (iSp4) decreased both basal and E2-induced transactivation. The contributions of individual Sp proteins to basal and E2-induced activity were promoter dependent, iSp1, iSp3, and iSp4 also significantly inhibited hormonal induction of E2F1, CAD, and RARα mRNA levels; however, the enhanced inhibitory effects of the latter two small inhibitory RNAs suggest that Sp3 and Sp4 play a major role in estrogen receptor α/Sp-mediated gene expression in MCF-7 cells.
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U2 - 10.1677/JME-07-0043
DO - 10.1677/JME-07-0043
M3 - Article
C2 - 17909268
AN - SCOPUS:35748937382
SN - 0952-5041
VL - 39
SP - 289
EP - 304
JO - Journal of molecular endocrinology
JF - Journal of molecular endocrinology
IS - 3-4
ER -