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Expression of Cytochromes P450 3A and P‐Glycoprotein in Human Large Intestinse in Paired Tumour and Normal Samples
Author(s) -
Canaparo Roberto,
Nordmark Anna,
Finnström Niklas,
Lundgren Stefan,
Seidegård Janeric,
Jeppsson Bengt,
Edwards Robert J.,
Boobis Alan R.,
Rane Anders
Publication year - 2007
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2006.00023.x
Subject(s) - p glycoprotein , cyp3a4 , messenger rna , microbiology and biotechnology , western blot , glycoprotein , biology , small intestine , gene expression , blot , cyp3a , chemistry , gene , metabolism , cytochrome p450 , biochemistry , multiple drug resistance , antibiotics
Our objective was to investigate the expression of different cytochromes P450 3A ( CYP3A4 , CYP3A5 , and CYP3A7 ) and P‐glycoprotein ( ABCB1 ) genes along the human large intestine in paired tumour and normal samples. Real‐time reverse transcriptase‐polymerase chain reaction was used to measure CYP3A4 ‐, CYP3A5 ‐, CYP3A7 ‐ and ABCB1 ‐specific mRNA expression, and Western blot analysis was used to measure membrane protein levels of CYP3A4/7, CYP3A5 and P‐glycoprotein. Levels of mRNA and membrane protein fractions in the large intestine were compared with those of normal human liver. The mRNA expressions of CYP3A4 , CYP3A5 , CYP3A7 and ABCB1 in the large intestine were found to be highly variable, but overall the levels were significantly lower than those measured in liver ( P < 0.0001, P < 0.001, P < 0.0001 and P < 0.01, respectively). At the membrane protein level, CYP3A4/7 was detected in all large intestine samples examined and the levels were substantially higher than those of the liver ( P < 0.01). Although expression of CYP3A5 was detected in all large intestine samples, in most the levels were too low to allow quantification. P‐glycoprotein was readily detected at levels slightly higher than those of liver ( P < 0.05). Comparison between paired samples of normal and tumour in large intestine showed no significant differences in either the mRNA or membrane protein levels of these genes. In conclusion, this work suggests a potential role of the large intestine in the absorption and metabolism of xenobiotics and nutrients and no difference in the CYP3A and P‐glycoprotein membrane protein fractions and mRNA expression between normal and tumour tissues.