Prostate cancer is a leading cause of death in men. In autopsy studies it is equally prevalent in all populations. Yet, clinical prostate cancer is less common than expected from the high autopsy incidence and more common in African-Americans as compared to White Americans. The key question is what factors contribute to activation of indolent to invasive cancer and might these behave differently in various populations. The long-term objective of the present study is to identify a biochemical marker that will be a predictor for prostate malignancy and ultimately a predictor to distinguish patients with indolent from those with invasive prostate cancer. We think the decrease in arachidonic acid (AA) levels in prostate cancer is due to increased AA turnover resulting in increased prostaglandin (PG) production. PGE/2 may be important in the early development and/or growth of prostate cancer. Lysophospholipid acyltransferase (LPAT) and phospholipase A/2 activities form an acylation- deacylation cycle important in phospholipid fatty acid remodeling, providing AA to tissues and releasing AA for PG production. Our hypothesis is that our recently demonstrated marked increase in LPAT activity, a biomarker of the increased AA metabolism in prostate cancer, will be a predictor of the presence of and invasiveness of prostate cancer.
Our specific aim i s to measure prostatic LPAT activity, AA levels, and 5alpha-reductase activity in a cohort of patients with benign prostatic hyperplasia, and suspected or documented prostate cancer. These measurements will be correlated with the presence or absence of malignancy and with the invasiveness of the disease. The biochemical analyses will be performed in prostatic tissue obtained from patients undergoing needle biopsy of the prostate, radical prostatectomy and transurethral resection of the prostate. Correlations will also be made between the prostatic LPAT activity, AA levels, and 5alpha-reductase activity; and racial status, serum and RBC fatty acid composition, serum PSA, testosterone, and DHEA-S, dietary factors and other demographic data.
| Faas, F H; Dang, A Q; White, J et al. (2001) Increased prostatic lysophosphatidylcholine acyltransferase activity in human prostate cancer: a marker for malignancy. J Urol 165:463-8 |
