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Cyclooxygenase-2 promotes prostate cancer progression
Hiroshi Fujita1, Kiyoshi Koshida, Evan T Keller
1Department of Urology, Kanazawa University, Kanazawa-City, Japan.
The Prostate
|October 19, 2002
Summary
Cyclooxygenase-2 (COX-2) promotes prostate cancer growth by increasing proliferation and tumor growth. This effect is partly mediated by enhanced vascular endothelial growth factor (VEGF) secretion, indicating COX-2
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cyclooxygenase-2 (COX-2) is expressed in prostate cancer and linked to tumor progression.
- COX-2 overexpression correlates with carcinogenesis, cell growth, angiogenesis, apoptosis, and invasiveness.
Purpose of the Study:
- To investigate the direct function of COX-2 in prostate cancer.
- To determine the mechanisms by which COX-2 influences prostate cancer growth.
Main Methods:
- Stable transfection of human full-length COX-2 cDNA into LNCaP cells (LNCaP-COX-2).
- Assessed COX-2 mRNA, protein levels, and COX activity.
- Evaluated cell proliferation in vitro and tumor growth in vivo.
- Measured androgen receptor (AR) expression and activity.
- Analyzed secretion of vascular endothelial growth factor (VEGF).
Main Results:
- COX-2 overexpression significantly increased COX-2 mRNA, protein, and activity in LNCaP-COX-2 cells.
- Overexpression of COX-2 enhanced both in vitro proliferation and in vivo tumor growth rate.
- The pro-tumor effects were independent of androgen receptor (AR) expression or activity.
- Increased secretion of vascular endothelial growth factor (VEGF) was observed, suggesting a role in angiogenesis.
Conclusions:
- COX-2 contributes to prostate cancer progression.
- COX-2 mediates its pro-tumor effects, in part, through increased VEGF secretion and subsequent angiogenesis.