Cytochrome P450 CYP3A in human renal cell cancer.
Renal cell cancer is the main malignant tumour of the kidney and has an increasing incidence. This type of tumour has a poor prognosis and shows intrinsic resistance to several anti-cancer drugs. The CYP3A P450 family, which consists of three closely related forms, is involved in the oxidative activation and deactivation of a variety of carcinogens and several anti-cancer drugs. In this study the presence and cellular localization of CYP3A has been investigated using a combination of immunohistochemistry, immunoblotting and reverse transcriptase polymerase chain reaction (RT-PCR) in renal cell cancer and corresponding normal kidney. CYP3A was consistently expressed in both renal call cancer and in normal kidney. In renal cell cancer, CYP3A was localized to tumour cells and in normal kidney the predominant cellular localization of CYP3A was to proximal tubular epithelial cells. RT-PCR showed that both CYP3A5 mRNA and CYP3A7 mRNA were consistently present in both tumour and normal samples, while CYP3A4 mRNA was present in 65% of tumours and 90% of normal samples. This study indicates that individual members of the CYP3A family are expressed in renal cell cancer. The presence of CYP3A in renal cell cancer might be important in the metabolic potentiation as well as the detoxification of chemotherapeutic agents used to renal cancer.
Murray
G I
GI
Department of Pathology, University of Aberdeen, Foresterhill, UK.
McFadyen
M C
MC
Mitchell
R T
RT
Cheung
Y L
YL
Kerr
A C
AC
Melvin
W T
WT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology; D007680:Kidney Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating