Correlation of repressed transcription of α-tocopherol transfer protein with serum α-tocopherol during hepatocarcinogenesis
✍ Scribed by Chuan-Ging Wu; Frans J. Hoek; Martijn Groenink; Pieter H. Reitsma; Sander J.H. van Deventer; Robert A.F.M. Chamuleau
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 295 KB
- Volume
- 71
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Using a subtraction-enhanced display technique, we identified a rodent a-tocopherol transfer protein (a-TTP) cDNA which exhibited markedly lower messenger RNA (mRNA) amounts in rat hepatocellular carcinoma (HCC) than in healthy controls. Several lines of evidence have substantiated that abnormal a-TTP results in isolated vitamin E deficiency. In this study, we investigated the hepatic mRNA amounts of a-TTP during rat hepatic carcinogenesis and liver regeneration on Northern blot, localization of a-TTP mRNA in HCC of rats and humans by in situ hybridization, and we analyzed the correlation between a-TTP mRNA and a-tocopherol. a-TTP mRNA concentrations of the rats were decreased at the early stage of hepatic carcinogenesis, and remained 3-5-fold reduced as the tumor progressed. In parallel, serum a-tocopherol concentrations were significantly decreased to 40% of those in the controls at the early stages of rat hepatic carcinogenesis (p F 0.01). The 2 data sets were strongly correlated (r 5 0.834, p F 0.001). In situ hybridization revealed that a decrease of a-TTP mRNA was preferentially localized in the tumor nodules of rats and humans with HCC. Our data suggest that repressed transcription of a-TTP is associated with a decrease of serum a-tocopherol and with hepatic carcinogenesis.