Reduction of dihydrodiol dehydrogenase expression in resected hepatocellular carcinoma.
Dihydrodiol dehydrogenase (DDH) is one of the major enzymes catabolizing polycyclic aromatic hydrocarbons in the liver. Although four DDH isoforms have been detected in the normal liver, only DDH1 and DDH2 have been detected in cancer cells of lung and esophagus. Moreover, the available information about hepatic pathophysiological regulation of DDH expression is limited. Therefore we addressed the question of DDH expression in patients with liver disorders, in particular, patients with hepatocellular carcinoma (HCC). Expression of DDH1/2 was determined by immunohistochemistry, immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR) in 52 patients with resected HCC. DDH1/2 expression was detected in 31 (59.6%) of 52 pathological sections. Frequency of DDH1/2 expression was significantly higher in patients with tumor size >2 cm, and in those who had early local recurrence. In addition to the tumor size and frequency of local recurrence, our results further indicated that expression of DDH1/2 was correlated with those of cyclooxygenase 2 (COX-2), interleukin-6 (IL-6), microsomal epoxide hydrolase (mEpH) and soluble epoxide hydrolase (sEpH) in HCC patients. Interestingly, the expression of DDH1/2 was found inversely correlated with that of glutathione S-transferase (GST) and NADPH p450 reductase (NPR). In conclusion, these results indicate that DDH expression was significantly decreased in about 40% of HCC patients. However, in the bordering non-neoplastic region of liver DDH1/2 expression increased, and the increased DDH1/2 expression correlated with tumor size and the disease progression.
Yang
Mei-Due
MD
Department of Surgery, China Medical College Hospital and Institute of Medical Science, China Medical College, Taichung, Taiwan.
Wu
Cheng-Chung
CC
Chiou
Shiow-Her
SH
Chiu
Chang-Fang
CF
Lin
Tze-Yi
TY
Chiang
I-Ping
IP
Chow
Kuan-Chih
KC
D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D051546:Cyclooxygenase 2; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006505:Hepatitis / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C048338:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; D009251:NADPH-Ferrihemoprotein Reductase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases