Concordant induction of 15-lipoxygenase-1 and mutant p53 expression in human prostate adenocarcinoma: correlation with Gleason staging

We recently reported that the mutant form of the tumor-suppressor gene p53 up-regulates 15-LO-1 gene expression in a murine cell line, Here, we examin e the expression of 15-lipoxygenase (LO)-1 and mutant p53 (mtp53) in human prostatic tissues and 15-LO-1 in the human prostate adenocarcinoma cell lin e PC-3, Reverse transcription-PCR and western analyses conclusively demonst rated expression of 15-LO-1 in PC-3 cells, Western blotting for 15-LO-1 in freshly resected 'normal' and prostate adenocarcinoma specimens showed 15-L O-1 expression in normal tissue, but significantly higher levels were detec ted in prostate adenocarcinomas, Prostate adenocarcinoma tissues generated chirally pure 13-S-hydroxyoctadecadienoic acid from exogenous linoleic acid , a preferred substrate of 15-LO-1. To study the correlation of 15-LO-1 exp ression with mtp53 in prostate cancer, we immunostained 48 prostatectomy sp ecimens obtained by transurethral resection of the prostate and needle biop sy (median age 68 years, range 52-93) of different Gleason grades (n = 48), using antibodies specific for 15-LO-1, mtp53 and MIB-1 (a proliferation ma rker), We compared staining in cancerous foci with adjacent normal appearin g prostate tissues, In only 5 of 48 patients did 'normal' tissue adjacent t o cancerous foci display staining for 15-LO-1, However, no staining for mtp 53 was observed in any of the normal tissues, In cancer foci, robust staini ng was observed for both 15-LO-1 (36 of 48, 75%) and mtp53 (19 of 48, 39%), Furthermore, the intensities of expression of 15-LO-1 and mtp53 correlated positively with each other (P < 0.001) and with the degree of malignancy, as assessed hy Gleason grading (P < 0.01). By immunohistochemistry, 15-LO-1 was located in secretory cells of peripheral zone glands, prostatic ducts and seminal vesicles, but not in the basal cell layer or stroma, Based on t hese and other studies, we propose a model describing a possible role for 1 5-LO-1 expression in influencing the malignant potential and pathobiologica l behavior of adenocarcinomas.