Cell context-dependent differences in the induction of E2F-1 gene expression by 17 beta-estradiol in MCF-7 and ZR-75 cells.
17 beta-Estradiol (E2) induces E2F-1 gene expression in ZR-75 and MCF-7 human breast cancer cells. Analysis of the E2F-1 gene promoter in MCF-7 cells previously showed that hormone-induced transactivation required interactions between estrogen receptor alpha (ER alpha)/Sp1 bound to upstream GC-rich sites and NFYA bound to downstream CCAAT sites within the -169 to -54 region of the promoter. This same region of the E2F-1 promoter was also E2 responsive in ER alpha-positive ZR-75 cells; however, further analysis of the promoter showed that cooperative ER alpha/Sp1/NFY interactions were not necessary for hormone-induced transactivation in ZR-75 cells. The upstream GC-rich motifs (-169 to -111) are activated independently by ER alpha/Sp1 in ZR-75 but not MCF-7 cells, and a construct (pE2F-1j(m1)) containing the -122 to -54 downstream CCAAT site that bound NFYA was also E2 responsive. E2 also induced reporter gene activity in ZR-75 cells transfected with an expression plasmid for a chimeric protein containing the DNA-binding domain of the yeast GAL4 protein fused to NFYA (pM-NFYA) and a construct containing five tandem GAL4 response elements. Subsequent studies showed that hormonal activation of pE2F-1j(m1) and pM-NFYA are dependent on nongenomic pathways in which E2 activates cAMP/protein kinase A. Hormone-dependent regulation of E2F-1 gene expression in ZR-75 and MCF-7 involves the same cis elements and interacting transcription factors but different mechanisms, demonstrating the importance of cell context on transactivation pathways, even among ER-positive breast cancer cell lines.
Ngwenya
Sharon
S
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-4466, USA.
Safe
Stephen
S
D023081:CCAAT-Binding Factor / Q000502:physiology; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000502:physiology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D011960:Receptors, Estrogen / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D014407:Tumor Cells, Cultured
D023081:CCAAT-Binding Factor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D047628:Estrogen Receptor alpha; C492061:NFYA protein, human; C492063:NFYB protein, human; D011960:Receptors, Estrogen; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D004958:Estradiol