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

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.

We used Atlas cDNA expression arrays from Clontech for initial screening, and quantitative real-time RT-PCR to assess the statistical significance of observed changes.

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 activator inhibitor-1 (PAI-1), insulin-like growth factor binding protein-3, and glyceraldehyde-3-phosphate dehydrogenase. Only PAI-1 was concordantly up-regulated in all four cell lines. Conversely, most down-regulated were the stress response genes, including several heat shock proteins, yet only the expression of flap endonuclease-1 was significantly decreased in all cell lines. When comparing individual cell lines, the HepG2 cells displayed a pattern of general down-regulation (83%), followed by Hep3B with 58% of genes down-regulated. In the Chang and HuH7 cells, however, the expression of most genes, 50% and 67%, respectively, remained unchanged.

These studies provide information that is of importance for improved insight into the responses of not only liver tumor cells but also normal liver tissue in the conditions where physiological oxygenation is severely impaired.