Correlation of repressed transcription of alpha-tocopherol transfer protein with serum alpha-tocopherol during hepatocarcinogenesis.

Abstract

Using a subtraction-enhanced display technique, we identified a rodent alpha-tocopherol transfer protein (alpha-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 alpha-TTP results in isolated vitamin E deficiency. In this study, we investigated the hepatic mRNA amounts of alpha-TTP during rat hepatic carcinogenesis and liver regeneration on Northern blot, localization of alpha-TTP mRNA in HCC of rats and humans by in situ hybridization, and we analyzed the correlation between alpha-TTP mRNA and alpha-tocopherol. alpha-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 alpha-tocopherol concentrations were significantly decreased to 40% of those in the controls at the early stages of rat hepatic carcinogenesis (p < 0.01). The 2 data sets were strongly correlated (r = 0.834, p < 0.001). In situ hybridization revealed that a decrease of alpha-TTP mRNA was preferentially localized in the tumor nodules of rats and humans with HCC. Our data suggest that repressed transcription of alpha-TTP is associated with a decrease of serum alpha-tocopherol and with hepatic carcinogenesis.

• Authors: C G Wu, F J Hoek, M Groenink, P H Reitsma, S J van Deventer, R A Chamuleau
• Journal: International journal of cancer (Int J Cancer) Vol. 71 Issue 4 Pg. 686-90 (May 16 1997) ISSN: 0020-7136 [Print] United States
• PMID: 9178827 (Publication Type: Journal Article)

Chemical References

• Carcinogens
• Carrier Proteins
• Neoplasm Proteins
• RNA, Messenger
• RNA, Neoplasm
• alpha-tocopherol transfer protein
• Vitamin A
• Vitamin E
• Diethylnitrosamine
• Cholesterol

Topics

• Aged
• Animals
• Carcinogens
• Carcinoma, Hepatocellular (chemistry, complications)
• Carrier Proteins (biosynthesis, genetics)
• Cholesterol (blood)
• Diethylnitrosamine
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hyperplasia
• Liver (drug effects, metabolism, pathology)
• Liver Neoplasms (chemistry, complications)
• Liver Neoplasms, Experimental (blood, chemically induced, genetics)
• Male
• Middle Aged
• Neoplasm Proteins (biosynthesis, genetics)
• RNA, Messenger (biosynthesis)
• RNA, Neoplasm (biosynthesis)
• Rats
• Rats, Wistar
• Transcription, Genetic
• Vitamin A (blood)
• Vitamin E (blood)
• Vitamin E Deficiency (etiology)