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  • Title: GATA-6 transcriptional regulation of 15-lipoxygenase-1 during NSAID-induced apoptosis in colorectal cancer cells.
    Author: Shureiqi I, Jiang W, Fischer SM, Xu X, Chen D, Lee JJ, Lotan R, Lippman SM.
    Journal: Cancer Res; 2002 Feb 15; 62(4):1178-83. PubMed ID: 11861401.
    Abstract:
    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.
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