Quantitative gene expression profiles of human liver-derived cell lines exposed to moderate hypoxia

Aims: To obtain better understanding of molecular events following critical oxygen shortage in liver tissue, we performed a large-scale comparison of gene expression profiles in four human liver cell lines, Chang, Hep3B, HuH7 , and HepG2. Methods: We used Atlas cDNA expression arrays from Clontech fo r initial screening, and quantitative real-time RT-PCR to assess the statis tical significance of observed changes. Results: RT-PCR analysis confirmed significantly changed levels of 24 transcripts after 24 hours incubation in 1% O-2. Among the genes most robustly up-regulated were plasminogen activa tor inhibitor-1 (PAI-1), insulin-like growth factor binding protein-3, and glyceraldehyde-3-phosphate dehydrogenase. Only PAI-1 was concordantly up-re gulated in all four cell lines. Conversely, most down-regulated were the st ress response genes, including several heat shock proteins, yet only the ex pression of flap endonuclease-1 was significantly decreased in all cell lin es. When comparing individual cell lines, the HepG2 cells di-splayed a patt ern of general down-regulation (83%), followed by Hep3B with 58% of genes d own-regulated. In the Chang and HuH7 cells, however, the expression of most genes, 50% and 67%, respectively, remained unchanged. Conclusion: These st udies provide information that is of importance for improved insight into t he responses of not only liver tumor cells but also normal liver tissue in the conditions where physiological oxygenation is severely impaired. Introd uction Copyright (C) 2001 S. Karger AG, Basel.