Cytochromes P450 are expressed in proliferating cells in Barrett's metaplasia.
The expression of cytochromes P450 (CYP) in Barrett's esophagus and esophageal squamous mucosa was investigated. Esophagectomy specimens from 23 patients were examined for CYP expression of CYP1A2, CYP3A4, CYP2C9/10, and CYP2E1 by immunohistochemical analysis, and the expression of CYP1A1, CYP3A4, CYP1B1, CYP2E1, and CYP2C9/10 in these tissues was further confirmed by reverse transcription polymerase chain reaction. Immunohistochemical analysis of esophageal squamous mucosa (n = 12) showed expression of CYP1A2, CYP3A4, CYP2E1, and CYP2C9/10 proteins, but it was noted that cells within the basal proliferative zone did not express CYPs. Immunohistochemical analysis of Barrett's esophagus (n = 13) showed expression of CYP1A2, CYP3A4, CYP2E1, and CYP2C9/10 that was prominent in the basal glandular regions, which are areas containing a high percentage of actively proliferating cells. Immunohistochemical staining for both proliferating cell nuclear antigen and the CYPs further supported the colocalization of CYP expression to areas of active cell proliferation in Barrett's esophagus, whereas in the esophageal squamous epithelium, CYP expression is limited to cells that are not proliferating. RT-PCR with amplification product sequence analysis confirmed CYP1A1, CYP3A4, CYP1B1, CYP2E1, and CYP2C9/10 mRNA expression in Barrett's esophagus. These data suggest that the potential ability of cells in Barrett's esophagus to both activate carcinogens and proliferate may be important risk factors affecting carcinogenesis in this metaplastic tissue.
Hughes
S J
SJ
Department of Surgery, University of Michigan Medical School, Ann Arbor, USA.
Morse
M A
MA
Weghorst
C M
CM
Kim
H
H
Watkins
P B
PB
Guengerich
F P
FP
Orringer
M B
MB
Beer
D G
DG
D001471:Barrett Esophagus / Q000201:enzymology*; D015153:Blotting, Western; D002455:Cell Division; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000737:chemistry; D004947:Esophagus / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D011230:Precancerous Conditions / Q000201:enzymology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018809:Proliferating Cell Nuclear Antigen; D020033:Protein Isoforms; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human