Effect of hypoxia on gene expression by human hepatocytes (HepG2)

• Published in: Physiological genomics Vol. 12; no. 3; pp. 195 - 207
• Main Authors: Sonna, Larry A, Cullivan, Michael L, Sheldon, Holly K, Pratt, Richard E, Lilly, Craig M
• Format: Journal Article
• Language: English
• Published: United States Am Physiological Soc 06.02.2003
• Subjects: Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Hypoxia - physiology; Chaperonins - genetics; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Heat-Shock Proteins - genetics; Humans; Oligonucleotide Array Sequence Analysis; Oxygen - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Temperature; Tumor Cells, Cultured
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00104.2002

1 Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick 01760 2 Division of Pulmonary and Critical Care Medicine 3 Cardiology Division and the Gene Array Technology Center, Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts 02115 The full extent to which hypoxia produces gene expression changes in human cells is unknown. We used late-generation oligonucleotide arrays to catalog hypoxia-induced changes in gene expression in HepG2 cells. Five paired sets of cultures were subjected to either control (room air-5% CO 2 ) or hypoxic (1% O 2 -5% CO 2 ) conditions for 24 h, and RNA was analyzed on an Affymetrix cDNA array containing 12,600 sequences. A statistically significant change in expression was shown by 2,908 sequences (1,255 increased and 1,653 decreased). The observed changes were highly concordant with published literature on hypoxic stress but showed relatively little overlap (12–22%) with changes in gene expression that have been reported to occur after heat stress in other systems. Of note, of these 2,908 sequences, only 387 (213 increased and 174 decreased) both exhibited changes in expression of twofold or greater and were highly expressed in at least three of the five experiments. We conclude that the effect of hypoxia on gene expression by HepG2 cells is broad, has a significant component of downregulation, and includes a relatively small number of genes whose response is truly independent of cell and stress type. cDNA array; hypoxic stress; cellular hypoxia; heat shock; cell stress response