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Role of PPAR-α on human liver metabolic dysfunction and carcinogenesis

Research Project

Project/Area Number 15591452
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionAICHI MEDICAL UNIVERSITY

Principal Investigator

KUROKAWA Tsuyoshi  AICHI MEDICAL UNIVERSITY, SURGERY, ASSOCIATE PROFESSOR, 医学部, 助教授 (50291406)

Co-Investigator(Kenkyū-buntansha) KOTAKE Katsuhiro  AICHI MEDICAL UNIVERSITY, SURGERY, ASSISTANT PROFESSOR, 医学部, 講師 (50351101)
NONAMI Toshiaki  AICHI MEDICAL UNIVERSITY, SURGERY, PROFESSOR, 医学部, 教授 (80189422)
SHIMOMURA Yoshiharu  NAGOYA INSTITUTE OF TECHNOLOGY, ENGINEERING, PROFESSOR, 工学部, 教授 (30162738)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsHEPATOCELLULAR CARCINOMA / PPAR-α / MITOCHONDRIA / LIVER CIRRHOSIS / CPT-1 / PPAR-α
Research Abstract

Background
Proliferator-activated receptor a (PPARα) regulates lipid metabolism in the liver. It is unclear, however, how PPARα changes in liver cancer tissue. On the other hand, from carcinogenesis experiments using mice, PPARα is necessary for development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer has been the focus of some attention. There have been no reports, however, on findings in human liver cancer.
Methods
The subjects were 10 patients who underwent hepatectomy for HCC. We assessed the expression of PPARα mRNA in human HCC tissue and non-cancerous tissue, as well as the expression of a target gene of PPARα, carnitine palmitoyltransferase 1A (CPT1A) and cyclin D1 mRNA. We also evaluated glyceraldehyde 3-phosphate dehydrogenase (G3PDH), a key enzyme in the glycolytic system.
Results
The amounts of PPARα, CPT1A and G3PDH mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of Cyclin D1 mRNA tend to be higher in cancerous sections than in non-cancerous sections. There was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections.
Conclusion
The present investigation of the levels of PPARα mRNA and mRNAs for PPARα target gene in human HCC and non-cancerous liver tissue suggest that lipids rather than carbohydrates may be mainly used for energy production in HCC, and that the inhibition of apoptosis via cyclin D may be linked to the development of cancer.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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