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

Abstract

Deletion analysis of several 17beta-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 alpha (RAR alpha) 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 RAR alpha 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 alpha/Sp-mediated gene expression in MCF-7 cells.

• Authors: Shaheen Khan, Fei Wu, Shengxi Liu, Qian Wu, Stephen Safe
• Journal: Journal of molecular endocrinology (J Mol Endocrinol) Vol. 39 Issue 4 Pg. 289-304 (Oct 2007) ISSN: 1479-6813 [Electronic] England
• PMID: 17909268 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• CAD trifunctional enzyme
• E2F1 Transcription Factor
• E2F1 protein, human
• Estrogen Receptor alpha
• Estrogens
• RARA protein, human
• Receptors, Retinoic Acid
• Retinoic Acid Receptor alpha
• Sp Transcription Factors
• Aspartate Carbamoyltransferase
• Dihydroorotase
• Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)

Topics

• Animals
• Aspartate Carbamoyltransferase (genetics)
• Breast Neoplasms (genetics, pathology)
• COS Cells
• Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) (genetics)
• Chlorocebus aethiops
• Dihydroorotase (genetics)
• E2F1 Transcription Factor (metabolism)
• Estrogen Receptor alpha (metabolism)
• Estrogens (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Receptors, Retinoic Acid (genetics, metabolism)
• Retinoic Acid Receptor alpha
• Sp Transcription Factors (metabolism, physiology)
• Tissue Distribution
• Tumor Cells, Cultured