title: Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-8655, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuzaka
authors.forename: Yuho
authors.initials: Y
authors.lastname: Najima
authors.forename: Motohiro
authors.initials: M
authors.lastname: Sekiya
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tomita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
authors.forename: Shin
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
mesh_terms: 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*
chemical_list: 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