INCREASED PROSTATIC LYSOPHOSPHATIDYLCHOLINE ACYLTRANSFERASE ACTIVITY IN HUMAN PROSTATE CANCER:: A MARKER FOR MALIGNANCY

Abstract

Purpose: Phospholipase A2 and lysophosphatidylcholine acyltransferase (LAT) constitute a deacylation-reacylation cycle that incorporates arachidonic acid into the lipid membrane. In a preliminary report we found increased LAT activity in malignant prostate tissue. We measured LAT activity in prostate tissue from a large number of patients undergoing prostatectomy. Materials and Methods: Prostate tissue from 93 patients undergoing radical prostatectomy for prostate carcinoma, 14 undergoing cystoprostatectomy for bladder cancer, 55 undergoing transurethral resection for benign prostatic hyperplasia and 11 with prostate cancer undergoing transurethral resection for relief of obstructive symptoms was analyzed for LAT activity. Results: In radical prostatectomy specimens using oleoyl coenzyme A as substrate mean increase in LAT activity between malignant and benign portions of the same specimen was 0.68 ± 0.12 nmol./mg. protein per minute (p <0.00001). In all radical prostatectomy specimens analyzed LAT activity was 43% higher in the malignant than benign portions (2.25 ± 0.15 versus 1.57 ± 0.11 nmol./mg. protein per minute, p <0.001). In the 10 benign prostate specimens obtained from cystoprostatectomy mean LAT activity was 1.12 ± 0.18 nmol./mg. protein per minute, which was significantly lower than that of benign portions of radical prostatectomy (p <0.05). LAT activity in benign cystoprostatectomy specimens was significantly higher than that in the 50 benign transurethral resection specimens (0.54 ± 0.05, p <0.01), possibly due to heat damage in transurethral resection specimens during collection. However, LAT activity in transurethral resection specimens from patients with known prostate cancer was similarly increased. Similar results were obtained using arachidonoyl coenzyme A. Conclusions: We demonstrated increased LAT activity in malignant tissue from patients with prostate cancer. Thus, the deacylation-acylation remodeling cycle may be enhanced to provide more arachidonic acid to meet the demand for prostaglandin E2 synthesis in malignant tissue.