Cytochrome P450 1B1 (CYP1B1) is overexpressed in human colon adenocarcinomas relative to normal colon: implications for drug development.
The cytochrome P450 family of enzymes is involved in the Phase I metabolism of a wide variety of compounds. Although generally involved with detoxification, overexpression of one family member, cytochrome P450 1B1 (CYP1B1), has been associated with human epithelial tumors. As such, CYP1B1 was hypothesized to be a novel target for the development of anticancer therapies. We investigated expression of CYP1B1 protein in 61 human colorectal adenocarcinomas and compared this to that observed in 14 histologically normal human large bowel samples removed from patients undergoing surgery for large bowel tumors. Although we confirmed that CYP1B1 was expressed at high levels in human colorectal tumor epithelia, we also found that CYP1B1 was not absent from normal colonic epithelia but was expressed at low levels. The expression of CYP1B1 in colon tumors does not correlate with tumor stage or degree of lymph node invasion in this study. Furthermore, in addition to expression in colon epithelia, CYP1B1 is also observed in blood vessels within the colon. As with the epithelia, levels of CYP1B1 were higher in tumor vasculature than that of the normal colon. Although these observations greatly support the development of CYP1B1 targeted anticancer therapies, they also indicate the caution that should be observed when developing such drugs.
Gibson
Paul
P
Cancer Research UK Laboratories, Tom Connors Cancer Research Centre, University of Bradford, Bradford BD7 1DP, United Kingdom.
Gill
Jason H
JH
Khan
Parveen A
PA
Seargent
Jill M
JM
Martin
Sandie W
SW
Batman
Philip A
PA
Griffith
John
J
Bradley
Christopher
C
Double
John A
JA
Bibby
Michael C
MC
Loadman
Paul M
PM
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000473:pathology; D065633:Cytochrome P-450 CYP1B1; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009130:Muscle, Smooth / Q000378:metabolism
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1