Role of specificity protein transcription factors in estrogen-induced gene expression in MCF-7 breast cancer cells

Abstract

Deletion analysis of several 17b-estradiol (E 2 )-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 E 2 -responsive GC-rich promoters from the E 2 F1, carbamoylphosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD), and retinoic acid receptor a (RARa) genes, RNA interference using small inhibitory RNAs for Sp1 (iSp1), Sp3 (iSp3), and Sp4 (iSp4) decreased both basal and E 2 -induced transactivation. The contributions of individual Sp proteins to basal and E 2 -induced activity were promoter dependent. iSp1, iSp3, and iSp4 also significantly inhibited hormonal induction of E 2 F1, CAD, and RARa 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 a/Sp-mediated gene expression in MCF-7 cells.

Metabolomics and Transcriptional Responses in Estrogen Receptor Positive Breast Cancer Cells

“…We found Sp3, but not Sp1, to be the major Sp protein activating the TFF1 upstream promoter region in response to E2 (Sun et al, 2005). This was supported by other studies where it was shown that Sp3 plays a major role in ER /Sp-mediated gene expression in MCF-7 cells (Khan et al, 2007). In general, Sp1 usually activates transcription and Sp3 represses or most weakly activates transcription (Higgins et al, 2006;Jaiswal et al, 2006;Noe et al, 2001).…”

“…In case of the p21 Waf1/Cip1 promoter, we also observed a lower Sp3 association in response to estrogen stimulation in MCF-7 cells (Mandal and Davie, 2007). We demonstrated that both Sp1 and Sp3 associated with TFF1, but Sp3, not Sp1, plays a major role in the estrogen activated ER /Sp-mediated gene expression in MCF-7 cells (Khan et al, 2007;Li and Davie, 2008). Therefore, in the context of estrogen stimulation, Sp1 and Sp3 play dual roles in regulating gene expression.…”

Inhibition of NFκB and Pancreatic Cancer Cell and Tumor Growth by Curcumin Is Dependent on Specificity Protein Down-regulation

“…The combined knockdown of Sp1, Sp3, and Sp4 (iSp) was the most effective treatment for decreasing p65 and p50 protein expression in L3.6pL cells. The differential effect of Sp1, Sp3, and Sp4 on regulation of other genes has also previously been reported in different cancer cell lines (22,(33)(34)(35). In addition, Sp knockdown also inhibited Panc28 and L3.6pL cell growth and induced PARP cleavage, indicating , and effects on Sp proteins, and p65 and p50 subunits of NFB were determined by Western blot analysis as described under "Experimental Procedures."…”

Multiple retinoic acid response elements cooperate to enhance the inducibility of CYP26A1 gene expression in liver

“…Non-RARE regions located between proximal and distal RAREs, which contain several SP1 and SP3 sites appear to play an important role in the basal promoter activity in HEK293T cells only, but in response to at-RA in both cell types. These transcriptional factors have been shown to interact with RARs in driving the expression of several genes in response to RA (Wolf et al, 2005; Khan et al, 2007; Laliotis et al, 2007; Islam et al, 2008; Zolfaghari and Ross, 2009). …”