Differences in cytochrome P450 2C19 (CYP2C19) expression in adjacent normal and tumor tissues in Chinese cancer patients.
BACKGROUND
Cytochrome P450 2C19 (CYP2C19) exhibits polymorphic expression in 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 various tumors and normal tissue adjacent to the tumor tissue in Han Chinese cancer patients.


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-quantitative RT-PCR Western immunoblots were also used to qualitatively assess CYP2C19 protein in the above tissues and cell lines.


RESULTS
CYP2C19 mRNA was found only in normal livers, hepatic carcinomas, and hepatocarcinoma cell 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, and the hepatocarcinoma cell lines HepG2, HepGA, and 7721 based on Western blotting methods. These results are in accordance with observations employing RT-PCR.


CONCLUSIONS
CYP2C19 mRNA expression is highest in hepatocarcinoma tissue, moderate in adjacent normal liver tissue, and absent in other cancer tissues and their adjacent normal tissues. The significantly elevated expression of CYP2C19 mRNA in hepatocarcinoma indicates an association between the occurrence of hepatocarcinoma and the expression and/or turnover of CYP2C19 mRNA.
Wu
Minliang
M
Department of Clinical Laboratory, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P R China.
Chen
Shuqing
S
Wu
Xiaohong
X
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D044466:Asian People; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19