Loss of TNF-α-regulated COX-2 expression in ovarian cancer cells

Wan Lin Yang, Isabelle H. Roland, Andrew K. Godwin, Xiang Xi Xu

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Cyclooxygenase 2 (COX-2) is often found overexpressed in cancer and is thought to have a role in carcinogenic promotion, and thus is a target for therapeutic intervention. Here, we investigated the regulation of COX-2 expression in normal and cancer ovarian surface epithelial cells. Tumor necrosis factor alpha (TNF-α) is a potent inducer of COX-2 expression in the ovarian surface epithelium and this regulation is a critical step in ovulation. We observed that TNF-α stimulated COX-2 expression in human primary and immortalized epithelial (HIO) cell lines. The stimulation was suppressed by inhibitors of several signaling pathways, indicating the collaboration of TNF-α-activated signaling pathways mediates the regulation of COX-2 expression. In five ovarian cancer cell lines analysed, four did not express detectable COX-2 and TNF-α failed to elicit COX-2 expression. In NIH:OVCAR-5, the only ovarian cancer cell line expressing COX-2, signal pathway inhibitors no longer affected TNF-α-induced COX-2 expression. Thus, we conclude that TNF-α mediated signaling is uncoupled from the modulation of COX-2 expression in ovarian cancer. The loss of COX-2 expression was also observed to associate closely with epithelial neoplastic morphological transformation. The frequent loss of COX-2 expression suggests in ovarian cancer, unlike in other epithelial cancers, COX-2 expression does not contribute to ovarian cancer malignancy.

Original languageEnglish (US)
Pages (from-to)7991-8002
Number of pages12
JournalOncogene
Volume24
Issue number54
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

Keywords

  • Cyclooxygenases
  • Ovarian carcinomas
  • Ovarian epithelial cells
  • TNF-α

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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