Journal article
Alterations in Lipoxygenase and Cyclooxygenase-2 Catalytic Activity and mRNA Expression in Prostate Carcinoma
Neoplasia (New York, N.Y.), Vol.3(4), pp.287-303
2001
DOI: 10.1038/sj.neo.7900166
PMCID: PMC1505867
PMID: 11571629
Abstract
Recent studies in prostate tissues and especially cell lines have suggested roles for arachidonic acid (AA) metabolizing enzymes in prostate adenocarcinoma (Pca) development or progression. The goal of this study was to more fully characterize lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) gene expression and AA metabolism in benign and malignant prostate using snap-frozen tissues obtained intraoperatively and mRNA analyses and enzyme assays. Formation of 15-hydroxyeicosatetraenoic acid (15-HETE) was detected in 23/29 benign samples and 15-LOX-2 mRNA was detected in 21/25 benign samples. In pairs of pure benign and Pca from the same patients, 15-HETE production and 15-LOX-2 mRNA were reduced in Pca versus benign in 9/14 (P=.04) and 14/17 (P=.002), respectively. Under the same conditions, neither 5HETE nor 12-HETE formation was detectable in 29 benign and 24 tumor samples; with a more sensitive assay, traces were detected in some samples, but there was no clear association with tumor tissue. COX-2 mRNA was detected by nuclease protection assay in 7/16 benign samples and 5/16 tumors. In benign and tumor pairs from 10 patients, COX-2 was higher in tumor versus benign in only 2, with similar results by in situ hybridization. Paraffin immunoperoxidase for COX2 was performed in whole mount sections from 87 additional radical prostatectomy specimens, with strong expression in ejaculatory duct as a positive control and corroboration with in situ hybridization. No immunostaining was detected in benign prostate or tumor in 45% of cases. Greater immunostaining in tumor versus benign was present in only 17% of cases, and correlated with high tumor grade (Gleason score 8 and 9 vs. 5 to 7). In conclusion, reduced 15-LOX-2 expression and 15-HETE formation is the most characteristic alteration of AA metabolism in Pca. Increased 12-HETE and 5-HETE formation in Pca were not discernible. Increased COX-2 expression is not a typical abnormality in Pca in general, but occurs in high-grade tumors.
Details
- Title: Subtitle
- Alterations in Lipoxygenase and Cyclooxygenase-2 Catalytic Activity and mRNA Expression in Prostate Carcinoma
- Creators
- Scott B Shappell - Department of Pathology, Vanderbilt University Medical Center, Nashville, TNSuzanne Manning - Department of Pathology, Vanderbilt University Medical Center, Nashville, TNWilliam E Boeglin - Department of Pharmacology, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TNYou-Fei Guan - Department of Medicine, Division of Nephrology and Veterans Affairs Hospital, Vanderbilt University Medical Center, Nashville, TNRichard L Roberts - Department of Pathology, Vanderbilt University Medical Center, Nashville, TNLinda Davis - Department of Medicine, Division of Nephrology and Veterans Affairs Hospital, Vanderbilt University Medical Center, Nashville, TNSandra J Olson - Department of Pathology, Vanderbilt University Medical Center, Nashville, TNGregory S Jack - Department of Pathology, Vanderbilt University Medical Center, Nashville, TNChristopher S Coffey - Department of Preventive Medicine, Vanderbilt University Medical Center, Nashville, TNThomas M Wheeler - Departments of Pathology and Urology, Baylor College of Medicine, Houston, TXMatthew D Breyer - Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TNAlan R Brash - Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
- Resource Type
- Journal article
- Publication Details
- Neoplasia (New York, N.Y.), Vol.3(4), pp.287-303
- DOI
- 10.1038/sj.neo.7900166
- PMID
- 11571629
- PMCID
- PMC1505867
- NLM abbreviation
- Neoplasia
- ISSN
- 1476-5586
- eISSN
- 1476-5586
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2001
- Academic Unit
- Biostatistics
- Record Identifier
- 9984214669402771
Metrics
28 Record Views