Cytoplasmic induction and over‐expression of cyclooxygenase‐2 in human prostate cancer: implications for prevention and treatment
Open Access
- 1 October 2000
- journal article
- research article
- Published by Wiley in BJU International
- Vol. 86 (6), 736-741
- https://doi.org/10.1046/j.1464-410x.2000.00867.x
Abstract
Objective To assess the level and morphological distribution of cyclooxygenase (COX)‐1 and ‐2 in human prostates and to determine any association with the Gleason grade of prostate cancer. Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX‐1 and ‐2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers). Results For both BPH and prostate cancer, COX‐1 expression was primarily in the fibromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX‐2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX‐2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX‐2 was unaltered, but expression by tumour cells was significantly greater (P = 0.008), with a change in the staining pattern from membranous to cytoplasmic (P < 0.001). COX‐2 expression was significantly higher in poorly differentiated than in well differentiated tumours (P < 0.001). These results were supported by immunoblotting, which showed similar levels of COX‐1 in both BPH and cancer, but four times greater expression of COX‐2 in cancer than in BPH. Conclusion This is the first study to assess the co‐expression of COX‐1 and COX‐2 proteins in benign and malignant human prostates, and showed the induction and significantly greater expression of COX‐2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti‐inflammatory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX‐2 inhibitors in the prevention and treatment of prostate cancer.Keywords
This publication has 20 references indexed in Scilit:
- Role of the Bcl-2 gene family in prostate cancer progression and its implications for therapeutic intervention.Environmental Health Perspectives, 1999
- Expression of bcl‐2 and p53 oncoproteins in schistosomiasis‐associated transitional and squamous cell carcinoma of urinary bladderBJU International, 1997
- NONSTEROIDAL ANTI-INFLAMMATORY DRUGS, EICOSANOIDS, AND COLORECTAL CANCER PREVENTIONGastroenterology Clinics of North America, 1996
- NSAID USE AND DECREASED RISK OF GASTROINTESTINAL CANCERSGastroenterology Clinics of North America, 1996
- Prostaglandin Endoperoxide H Synthases-1 and -2Advances in Immunology, 1996
- Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2Cell, 1995
- Arachidonic acid metabolism in benign and malignant prostatic tissue in vitro: Effects of fatty acids and cyclooxygenase inhibitorsInternational Journal of Cancer, 1994
- Dietary fat, fatty acids and prostate cancerLipids, 1992
- Bioactivation of xenobiotics by prostaglandin H synthaseChemico-Biological Interactions, 1991
- Relevance of fatty acids and eicosanoids to clinical and preventive medicineProgress in Lipid Research, 1986