Attenuation of c-Jun and Sp1 expression and p300 recruitment to gene promoter confers the trichostatin A-induced inhibition of 12(S)-lipoxygenase expression in EGF-treated A431 cells

Ching Jiunn Chen, Wen Chang Chang, Ben Kuen Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The mechanism by which the histone deacetylase (HDAC) inhibitor trichostatin A inhibits epidermal growth factor (EGF)-induced human 12(S)-lipoxygenase expression was studied. Trichostatin A treatment of human epidermoid carcinoma A431 cells inhibited the EGF-induced 12(S)-lipoxygenase enzymatic activity in a dose-dependent manner that was consistent with the expression of 12(S)-lipoxygenase mRNA and protein. Confocal microscopy indicated that trichostatin A treatment of cells resulted in downregulation of EGF-induced c-Jun expression. Western blotting revealed that trichostatin A treatment of cells resulted in downregulation of EGF-induced c-Jun and constitutively Sp1 expression. Results of a chromatin immunoprecipitation assay revealed that trichostatin A treatment of cells also upregulated Sp1 acetylation and attenuated the recruitment of Sp1, c-Jun, and p300 to the 12(S)-lipoxygenase gene promoter. These results suggested that trichostatin A inhibited EGF-induced 12(S)-lipoxygenase expression by multiple mechanisms, including the attenuation of c-Jun and Sp1 expression and p300 recruitment to the 12(S)-lipoxygenase gene promoter.

Original languageEnglish
Pages (from-to)36-42
Number of pages7
JournalEuropean Journal of Pharmacology
Volume591
Issue number1-3
DOIs
Publication statusPublished - Sep 4 2008
Externally publishedYes

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Keywords

  • 12(S)-lipoxygenase
  • c-Jun
  • Epidermal growth factor
  • p300
  • Sp1
  • Trichostatin A

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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