Role of SP transcription factors in hormone-dependent modulation of genes in MCF-7 breast cancer cells: Microarray and RNA interference studies

Fei Wu, Ivan Ivanov, Rui Xu, Stephen Safe

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

17β-Estradiol (E2) binds estrogen receptor α (ESR1) in MCF-7 cells and increases cell proliferation and survival through induction or repression of multiple genes. ESR1 interactions with DNA-bound specificity protein (SP) transcription factors is a nonclassical genomic estrogenic pathway and the role of SP transcription factors in mediating hormone-dependent activation or repression of genes in MCF-7 cells was investigated by microarrays and RNA interference. MCF-7 cells were transfected with a nonspecific oligonucleotide or a cocktail of small inhibitory RNAs (iSP), which knockdown SP1, SP3, and SP4 proteins, and treated with dimethylsulfoxide or 10 nM E2 for 6 h. E2 induced 62 and repressed 134 genes and the induction or repression was reversed in ∼62% of the genes in cells transfected with iSP (ESR1/SP dependent), whereas hormonal activation or repression of the remaining genes was unaffected by iSP (SP independent). Analysis of the ESR1/SP-dependent and SP-independent genes showed minimal overlap with respect to the GO terms (functional processes) in genes induced or repressed, suggesting that the different genomic pathways may contribute independently to the hormone-induced phenotype in MCF-7 cells.

Original languageEnglish (US)
Pages (from-to)19-33
Number of pages15
JournalJournal of Molecular Endocrinology
Volume42
Issue number1
DOIs
StatePublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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