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 language | English (US) |
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Pages (from-to) | 7991-8002 |
Number of pages | 12 |
Journal | Oncogene |
Volume | 24 |
Issue number | 54 |
DOIs | |
State | Published - Dec 1 2005 |
Externally published | Yes |
Keywords
- Cyclooxygenases
- Ovarian carcinomas
- Ovarian epithelial cells
- TNF-α
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics