Cell context-dependent differences in the induction of E2F-1 gene expression by 17β-estradiol in MCF-7 and ZR-75 cells

Sharon Ngwenya, Stephen Safe

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

17β-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 α (ERα)/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 ERα-positive ZR-75 cells; however, further analysis of the promoter showed that cooperative ERα/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 ERα/Sp1 in ZR-75 but not MCF-7 cells, and a construct (pE2F-1jm1) 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-1jm1 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.

Original languageEnglish (US)
Pages (from-to)1675-1685
Number of pages11
JournalEndocrinology
Volume144
Issue number5
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Endocrinology

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