Identification of cytochrome P450 enzymes in human colorectal metastases and the surrounding liver: a proteomic approach.
We describe the direct identification of multiple cytochrome P450 (CYP) enzymes in healthy and cancerous tissue. CYPs in human liver colorectal metastases were compared with those in the surrounding liver using a mass spectrometry-based proteomic approach. Nano-scale reversed phase liquid chromatography combined with electrospray ionisation tandem mass spectrometry has been used to identify CYPs with no pre-selection of the proteins anticipated. Fourteen distinct CYP enzymes from the subfamilies 1A, 2A, 2B, 2C, 2D, 2E, 3A, 4A, 4F, 8B and 27A were positively identified; 13 in the liver samples and 12 in the tumour tissue. It was found that three of the colorectal metastases expressed essentially the same drug-metabolising pattern of CYPs as the surrounding liver, whilst three tumour samples from different individuals showed no CYP expression. This was likely in at least one case to be due to low sample mass. The CYP expression profile in an individual tumour is likely to be an important determinant in predicting the outcome of cancer chemotherapy.
Lane
C S
CS
Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29/39 Brunswick Square, WC1N 1AX, UK.
Nisar
S
S
Griffiths
W J
WJ
Fuller
B J
BJ
Davidson
B R
BR
Hewes
J
J
Welham
K J
KJ
Patterson
L H
LH
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000556:secondary; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D020543:Proteome / Q000378:metabolism
D020543:Proteome; D003577:Cytochrome P-450 Enzyme System