Abstract |
Normal and malignant hepatocytes were transfected during log phase culture with a nested series of DNA plasmids containing 5'-flanking regions of the rat liver-specific acute phase plasma proteinase alpha 1-inhibitor III (alpha 1 I3) gene. Under these conditions, luciferase reporter gene expression in primary adult rat and mouse hepatocytes was 10-fold higher than luciferase expression in hepatoma lines (human HepG2 and Hep3B; rat FAZA). Optimal expression in primary rat hepatocytes required regions stretching 2214 bp 5'-upstream of the transcription start site. Shorter 5'-flanking sequences were optimal for expression in hepatoma cells (-1025 and -186 bp for rat and human lines, respectively) and primary mouse hepatocytes (-225 bp). In contrast, regions from -186 to -225 bp drove luciferase expression in primary rat hepatocytes, but only 20-75% of optimal levels. Qualitative differences were unaccounted for by non-equivalent uptake of plasmid DNA, suggesting that tissue specific gene expression is regulated differently in normal and malignant cells, and with apparent species specificity.
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Authors | K S Koch, X P Lu, D A Brenner, H L Leffert |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 183
Issue 1
Pg. 184-92
(Feb 28 1992)
ISSN: 0006-291X [Print] United States |
PMID | 1543489
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Acute-Phase Proteins
- Blood Proteins
- Protease Inhibitors
- Recombinant Fusion Proteins
- Transforming Growth Factor alpha
- alpha 1-inhibitor 3
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Topics |
- Acute-Phase Proteins
- Animals
- Blood Proteins
(genetics)
- Cells, Cultured
- Gene Expression Regulation, Neoplastic
(drug effects)
- Liver
(cytology, metabolism)
- Liver Neoplasms, Experimental
(metabolism)
- Male
- Protease Inhibitors
(metabolism)
- Rats
- Recombinant Fusion Proteins
- Regulatory Sequences, Nucleic Acid
(genetics)
- Transfection
- Transforming Growth Factor alpha
(pharmacology)
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