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 |
|---|---|
| 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 |
Fingerprint
Keywords
- Cyclooxygenases
- Ovarian carcinomas
- Ovarian epithelial cells
- TNF-α
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Loss of TNF-α-regulated COX-2 expression in ovarian cancer cells. / Yang, Wan Lin; Roland, Isabelle H.; Godwin, Andrew K.; Xu, Xiangxi.
In: Oncogene, Vol. 24, No. 54, 01.12.2005, p. 7991-8002.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Loss of TNF-α-regulated COX-2 expression in ovarian cancer cells
AU - Yang, Wan Lin
AU - Roland, Isabelle H.
AU - Godwin, Andrew K.
AU - Xu, Xiangxi
PY - 2005/12/1
Y1 - 2005/12/1
N2 - 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.
AB - 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.
KW - Cyclooxygenases
KW - Ovarian carcinomas
KW - Ovarian epithelial cells
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=28544440746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28544440746&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208943
DO - 10.1038/sj.onc.1208943
M3 - Article
C2 - 16044148
AN - SCOPUS:28544440746
VL - 24
SP - 7991
EP - 8002
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 54
ER -