Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.
Hepatocellular carcinoma is a very common neoplastic disease in countries where hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma lesions detected by ultrasonography at an early stage are often hyperechoic because they are composed of well-differentiated cancer cells that are rich in triglyceride droplets. The triglyceride content of hepatocytes depends in part on the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are co-ordinately regulated at the transcriptional level. We therefore examined the mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples from 10 patients who had undergone surgical resection. All of the samples exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with surrounding non-cancerous liver tissue. In contrast, the changes in mRNA expression of SREBP-1, a transcription factor that regulates a battery of lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1 was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a. Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in some cases SREBP-1c is involved in this activation.
Yahagi
Naoya
N
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-8655, Japan.
Shimano
Hitoshi
H
Hasegawa
Kiyoshi
K
Ohashi
Kenichi
K
Matsuzaka
Takashi
T
Najima
Yuho
Y
Sekiya
Motohiro
M
Tomita
Sachiko
S
Okazaki
Hiroaki
H
Tamura
Yoshiaki
Y
Iizuka
Yoko
Y
Ohashi
Ken
K
Nagai
Ryozo
R
Ishibashi
Shun
S
Kadowaki
Takashi
T
Makuuchi
Masatoshi
M
Ohnishi
Shin
S
Osuga
Jun-ichi
J
Yamada
Nobuhiro
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D003067:Coenzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D004798:Enzymes / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D003067:Coenzymes; D004268:DNA-Binding Proteins; D004798:Enzymes; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides