GATA-6 transcriptional regulation of 15-lipoxygenase-1 during NSAID-induced apoptosis in colorectal cancer cells

Imad Shureiqi, Wei Jiang, Xiaochun Xu, Dongning Chen, Scott M. Lippman, Imad Shureiqi, Susan M. Fischer, J. Jack Lee, Reuben Lotan

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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-I 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 Ectople 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.

Original languageEnglish (US)
Pages (from-to)1178-1183
Number of pages6
JournalCancer Research
Volume62
Issue number4
StatePublished - Feb 15 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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