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.
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.
Chen
Ching-Jiunn
CJ
Department of Medical Technology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, Taiwan. charles2@ms34.url.com.tw
Chang
Wen-Chang
WC
Chen
Ben-Kuen
BK
D001092:Arachidonate 12-Lipoxygenase / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004305:Dose-Response Relationship, Drug; D050881:E1A-Associated p300 Protein / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; C012589:trichostatin A; D004815:Epidermal Growth Factor; D001092:Arachidonate 12-Lipoxygenase; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human