CYP1B1 expression in prostate is higher in the peripheral than in the transition zone Narasimhan Ragavan a,b , Rebecca Hewitt a , Leanne J. Cooper a , Katherine M. Ashton b , Andrew C. Hindley b , Caroline M. Nicholson b , Nigel J. Fullwood a , Shyam S. Matanhelia b , Francis L. Martin a, * a Department of Biological Sciences, IENS, Lancaster University, Lancaster LA1 4YQ, UK b Lancashire Teaching Hospitals, NHS Trust, Preston PR2 9HT, UK Received 5 May 2004; received in revised form 27 June 2004; accepted 29 June 2004 Abstract Prostate cancer (CaP) mostly occurs in the peripheral zone whereas benign prostatic hypertrophy (BPH) occurs in the transition zone. Human prostates (nZ12) were obtained, with ethical approval, from radical retropubic prostatectomies. Following resection, tissue sets consisting of peripheral zone and transition zone were isolated from a lobe pre-operatively identified as negative for CaP. Real-time RT-PCR was employed to quantitatively examine CYP1A1, CYP1A2 and CYP1B1. Quantifiable CYP1A1 expression was observed (in nine out of twelve tissue sets) whilst CYP1A2 mRNA transcripts, although detectable (in six out of twelve tissue sets), were unquantifiable. In ten tissue sets, 2- to 6-fold higher CYP1B1 expression in peripheral zone as compared to transition zone was observed. In the other two, equal CYP1B1 expression levels were observed; retrospective examination identified malignancy in one of the zones. Inter-individual variations (up to 10-fold) in CYP1B1 were also noted. Immunohistochemistry for CYP1B1 showed epithelial and stromal nuclear staining. Since CYP1B1 metabolises hormones and carcinogens our results, if confirmed, suggest that this enzyme may influence susceptibility to CaP. q 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: CYP1B1; Human prostate; Nuclear staining; Peripheral zone; Radical retropubic prostatectomy; Transition zone 1. Introduction Although only a small acorn-shaped gland (w50 g) in the genitourinary tract, the human prostate is the most common site of pathology in the male [1]. Situated beneath the bladder and surrounding the urethra, it is a composite organ consisting of non- glandular (fibromuscular) and glandular components [2]. Using the urethra as the key anatomical reference 0304-3835/$ - see front matter q 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.canlet.2004.06.051 Cancer Letters 215 (2004) 69–78 www.elsevier.com/locate/canlet Abbreviations: BPH, benign prostatic hypertrophy; BSAT, 0.2% bovine serum albumin in Tris-buffered saline (pH 7.6); CaP, prostate cancer; DAB, 3,3 0 -diaminobenzidine; DRE, digital rectal examination; HAAs, heterocyclic aromatic amines; NV, non- vegetarian; PAHs, polycyclic aromatic hydrocarbons; PSA, prostate specific antigen; RT, reverse transcriptase; TBS, tris-buffered saline. * Corresponding author. Tel.: C44-1524-594505; fax: C44- 1524-843854. E-mail address: f.martin@lancaster.ac.uk (F.L. Martin).