GATA-6 transcriptional regulation of 15-lipoxygenase-1 during NSAID-induced apoptosis in colorectal cancer cells.
The mechanisms by which nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in colorectal cancer cells are undergoing intensive investigation. We found previously that NSAIDs induce apoptosis in these cells by restoring 15-lipoxygenase-1 (15-LOX-1) expression. The present study examined the NSAID mechanism for up-regulating 15-LOX-1 in two colorectal cancer cell lines (RKO and DLD-1). We found that NSAID effects on 15-LOX-1 occurred at the level of transcriptional regulation. We then studied NSAID effects on GATA-6, a transcription factor that suppresses 15-LOX-1 expression. Beginning within 4 h, NSAIDs progressively down-regulated GATA-6 expression. Ectopic GATA-6 expression blocked NSAID induction of 15-LOX-1 and apoptosis. NSAIDs down-regulate GATA-6 to transcriptionally up-regulate 15-LOX-1 and induce apoptosis in colorectal cancer cells.
Shureiqi
Imad
I
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA. ishureiqi@mdanderson.org
Jiang
Wei
W
Fischer
Susan M
SM
Xu
Xiaochun
X
Chen
Dongning
D
Lee
J Jack
JJ
Lotan
Reuben
R
Lippman
Scott M
SM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D050993:GATA6 Transcription Factor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D013467:Sulindac / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D014157:Transcription Factors; D013467:Sulindac; D001093:Arachidonate 15-Lipoxygenase