Decreased expression of cytochrome P450 protein in non-malignant colonic tissue of patients with colonic adenoma.
BACKGROUND
Cytochrome P450 (CYP) enzymes in epithelial cells lining the alimentary tract play an important role in both the elimination and activation of (pro-)carcinogens. To estimate the role of cytochrome P450 in carcinogenesis of the colon, expression patterns and protein levels of four representative CYPs (CYP2C, CYP2E1, CYP3A4 and CYP3A5) were determined in colon mucosa of normal and adenomatous colonic tissue of patients with adenomas and disease-free controls.


METHODS
Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 in colon mucosa of normal and adenomatous colonic tissue of patients with adenoma and disease-free controls was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot.


RESULTS
With the exception of CYP3A5, expression of CYP mRNA was similar among groups and tissues (e.g. normal colon mucosa and adenoma). CYP3A5 mRNA expression was significantly higher in adenoma in comparison to normal tissue of patients with adenoma (approximately 48%). When comparing protein concentrations of CYPs measured in adenomas with neighboring normal colonic mucosa no differences were found. However, in normal tissue of patients with adenomas, protein levels of CYP2C8, CYP3A4 and CYP3A5, but not that of CYP2E1, were significantly lower than in biopsies obtained from disease-free controls. Specifically, in normal colonic mucosa of patients protein concentrations of CYP2C8, CYP3A4, and CYP3A5 were approximately 86%, approximately 69%, and approximately 54%, respectively, lower than in disease-free controls.


CONCLUSIONS
In conclusion, among other factors, the altered protein levels of certain CYPs (e.g. CYP2C8, CYP3A4 and CYP3A5) in colon mucosa might contribute to the development of neoplasia in the colon.
Bergheim
Ina
I
Department Physiology of Nutrition, Hohenheim University (140), Stuttgart, Germany. ina.bergheim@freenet.de
Bode
Christiane
C
Parlesak
Alexandr
A
D000236:Adenoma / Q000201:enzymology*; D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D003106:Colon / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000201:enzymology*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D008875:Middle Aged; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D012333:RNA, Messenger; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human