Fatty acid-CoA ligase 4 is overexpressed in human hepatocellular carcinoma.
Fatty acid-CoA ligase 4 (FACL4) is a central enzyme controlling the unesterified arachidonic acid (AA) level in cells. It has been shown that FACL4 blocks apoptosis and promotes colon carcinogenesis by lowering the cellular level of unesterified AA. Consistent with this, FACL4 is upregulated in colon adenocarcinoma. The status of FACL4 in other tumors including hepatocellular carcinoma (HCC) is not known. Here, we report that FACL4 is overexpressed in human HCC compared with adjacent normal liver tissues. FACL4 mRNA and protein were overexpressed in 5 out of 12 (41.7%) and 3 out of 8 (37.5%) cases of HCC, respectively. Immunohistochemical staining showed strong fine granular intracytoplasmic staining in tumor cells, whereas we observed occasional weak staining in normal liver tissues surrounding the tumors. We found that 14 out of 37 (37.8%) HCC expressed moderate to strong FACL4 immunostaining. Both normal adult and fetal liver tissues showed very weak to no detectable staining, whereas 3 out of 10 (30%) cirrhotic livers expressed weak staining. In addition, we found that 4 out of 8 (50%) human hepatoma cell lines expressed high levels of FACL4 by northern blot analysis. Our results show that FACL4 is a new molecular marker for HCC and suggest that the FACL4 pathway may be involved in liver carcinogenesis.
Sung
Young Kwan
YK
Department of Immunology, Kyungpook National University Medical School and Hospital, Daegu, 700-422, Korea.
Hwang
Sun Young
SY
Park
Mi Kyung
MK
Bae
Han Ik
HI
Kim
Woo Ho
WH
Kim
Jung-Chul
JC
Kim
Moonkyu
M
D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D003066:Coenzyme A Ligases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm; D011817:Rabbits; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D014408:Biomarkers, Tumor; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase