Differences in cytochrome P450 2C19 (CYP2C19) expression in adjacent normal and tumor tissues in chinese cancer patients.
Minliang Wu, Shuqing Chen, Xiaohong Wu
Med Sci Monit 2006; 12(5): BR174-178
Background: Cytochrome P450 2C19 (CYP2C19) exhibits polymorphic expressionin humans and deficiencies in its expression have been associated with a number of different cancers.Our aim was to determine if CYP2C19 mRNA and CYP2C19 enzyme protein expression differed between varioustumors and normal tissue adjacent to the tumor tissue in Han Chinese cancer patients. Material/Methods:The level of CYP2C19 mRNA expression was examined in tumor and adjacent normal tissue from liver, colon,stomach, breast, esophagus, lung, uterus, brain, pancreas, ovary, kidney, and several cell lines by semi-quantitativeRT-PCR. Western immunoblots were also used to qualitatively assess CYP2C19 protein in the above tissuesand cell lines. Results: CYP2C19 mRNA was found only in normal livers, hepatic carcinomas, and hepatocarcinomacell lines. The CYP2C19 mRNA was expressed at significantly higher levels in hepatocellular carcinomas(x+/-s: 3.72+/-1.21, n=14) than in adjacent normal liver tissue (x+/-s: 1.79+/-0.33, n=14,p=0.000). CYP2C19 protein was also detected in hepatocarcinoma tissues, adjacent normal tissues, andthe hepatocarcinoma cell lines HepG2, HepGA, and 7721 based on Western blotting methods. These resultsare in accordance with observations employing RT-PCR. Conclusions: CYP2C19 mRNA expression is highestin hepatocarcinoma tissue, moderate in adjacent normal liver tissue, and absent in other cancer tissuesand their adjacent normal tissues. The significantly elevated expression of CYP2C19 mRNA in hepatocarcinomaindicates an association between the occurrence of hepatocarcinoma and the expression and/or turnoverof CYP2C19 mRNA.
Keywords: Humans, Reverse Transcriptase Polymerase Chain Reaction, RNA, Neoplasm - metabolism, RNA, Messenger - metabolism, Neoplasms - genetics, Mixed Function Oxygenases - metabolism, Male, Liver Neoplasms - genetics, Liver - enzymology, Base Sequence, Gene Expression, Female, DNA, Complementary - genetics, Carcinoma, Hepatocellular - genetics, Blotting, Western, Aryl Hydrocarbon Hydroxylases - metabolism, Asian Continental Ancestry Group