TY - JOUR

T1 - Inter-and intra-individual variations in prostate CYP1B1 expression suggest a role in peripheral-zone susceptibility to adenocarcinoma.

AU - Ragavan, Narasimhan

AU - Hewitt, Rebecca

AU - Hindley, Andrew C.

AU - Nicholson, C. M.

AU - Matanhelia, Shyam S.

AU - Martin, Francis L.

PY - 2004/11

Y1 - 2004/11

N2 - The prostate is conventionally divided into zones. Prostate adenocarcinoma (CaP) is commonly confined to the peripheral zone. Cytochrome P-450 (CYP) isoenzymes are constitutively expressed and inducible enzymes, many of which are involved in hormone and carcinogen hydroxylation. These include the CYP1A1, CYP1A2 and CYP1B1 isoforms. Human prostates (n 5 12) were obtained, with ethical approval, from radical retropubic prostatectomies. Study participants exhibited low PSA (520 mg/l serum) and low volume of disease (5two/eight core biopsies positive for CaP). 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. CYP1A1 expression was quantifiable in either or both zones of nine tissue sets and was unquantifiable in three others. In six tissue sets, higher levels of CYP1A1 expression were observed in the transition zone compared to the peripheral zone. CYP1A2, although detectable, was not quantifiably expressed. CYP1B1 expression was detected in both zones of all tissue sets examined. Interindividual variation in CYP1B1 expression levels in peripheral zone (0.5--2-fold) and transition zone (0.5--5-fold) were noted. In ten tissue sets found to be cancer free, CYP1B1 expression was 2- to 6-fold higher in the peripheral zone compared to the transition zone. In the remaining two tissue sets, CYP1B1 expression was approximately equal in both zones; histopathology showed CaP in one of the zones. CYP1B1 preferentially catalyses the 4-hydroxylation of 17b-oestradiol, metabolically activates exogenous procarcinogens and inactivates anticancer agents. Our results suggest that CYP1B1 may influence susceptibility to CaP.

AB - The prostate is conventionally divided into zones. Prostate adenocarcinoma (CaP) is commonly confined to the peripheral zone. Cytochrome P-450 (CYP) isoenzymes are constitutively expressed and inducible enzymes, many of which are involved in hormone and carcinogen hydroxylation. These include the CYP1A1, CYP1A2 and CYP1B1 isoforms. Human prostates (n 5 12) were obtained, with ethical approval, from radical retropubic prostatectomies. Study participants exhibited low PSA (520 mg/l serum) and low volume of disease (5two/eight core biopsies positive for CaP). 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. CYP1A1 expression was quantifiable in either or both zones of nine tissue sets and was unquantifiable in three others. In six tissue sets, higher levels of CYP1A1 expression were observed in the transition zone compared to the peripheral zone. CYP1A2, although detectable, was not quantifiably expressed. CYP1B1 expression was detected in both zones of all tissue sets examined. Interindividual variation in CYP1B1 expression levels in peripheral zone (0.5--2-fold) and transition zone (0.5--5-fold) were noted. In ten tissue sets found to be cancer free, CYP1B1 expression was 2- to 6-fold higher in the peripheral zone compared to the transition zone. In the remaining two tissue sets, CYP1B1 expression was approximately equal in both zones; histopathology showed CaP in one of the zones. CYP1B1 preferentially catalyses the 4-hydroxylation of 17b-oestradiol, metabolically activates exogenous procarcinogens and inactivates anticancer agents. Our results suggest that CYP1B1 may influence susceptibility to CaP.

U2 - 10.1093/mutage/geh052

DO - 10.1093/mutage/geh052

M3 - Journal article

VL - 19

SP - 503

JO - Mutagenesis

JF - Mutagenesis

SN - 1464-3804

IS - 6

ER -