EXPRESSION OF HORMONE-/CARCINOGEN-METABOLISING ENZYMES IN THE PROSTATE: CLUES INTO PERIPHERAL-ZONE SUSCEPTIBILITY?

Abstract

INTRODUCTION & OBJECTIVES: The peripheral zone (PZ) of the prostate presents with a higher occurrence of adenocarcinoma (CaP) compared to transition zone (TZ). Environmental procarcinogens and endogenous hormones implicated in the aetiology, often requires bio-activation to DNA-binding species (that form DNA-carcinogen adducts) which are done by phase I cytochrome P-450 (CYP) isoenzymes (CYP1A1, CYP1A2 and CYP1B1) and, the phase II N-acetyl transferases (NAT1 and NAT2) and catechol-O-methyl transferase (COMT). The objective of this study is to assess intra- (PZ vs. TZ) and inter-individual variations in the gene expression of phase I and II enzymes using quantitative real-time RT-PCR in CaP-free tissues. MATERIAL & METHODS: With ethical approval, prostate tissue sets (PZ and TZ) (n=27) were obtained from patients (inclusion criteria - low PSA (<20 mg/l serum) and/or low volume disease ≤two/eight core biopsies positive for CaP)) undergoing radical prostatectomy, isolated from a lobe preoperatively identified as negative for CaP. Real-time RT-PCR was employed to quantitatively examine CYP1A1, CYP1A2, CYP1B1, NAT1, NAT2 and COMT. Immunohistochemistry (with polyclonal anti-CYP1B1 antibody) was employed to assess CYP1B1 protein and location in the prostate. In all cases, retrospective analysis (after HE some nuclear staining was also observed in the stroma. In CaP tissue, sheaths of cells exhibiting both nuclear staining and cytoplasmic staining were observed. CONCLUSIONS: Our study demonstrates the expression in the prostate of phase I and II enzymes. And CYP1B1 expression is particularly high in peripheral zone. Its role as a target either for chemoprevention/treatment strategies remains to be investigated.