Identification of genes differentially expressed by hypoxia in hepatocellular carcinoma cells.

In order to identify genes differentially expressed under hypoxia (1% O2, 5% CO2, balance N2), we performed mRNA differential display analysis using total RNA extracted from hypoxic and normoxic HepG2, human hepatocellular carcinoma (HCC) cells. Of the differentially expressed genes by hypoxia, some of cDNA fragments were cloned and sequenced. The expression patterns of these clones by hypoxia were confirmed by Northern blot analysis and the quantitative RT-PCR. Down-regulated genes by hypoxia have homology to cDNA sequences encoding cytochrome oxidase subunit II and ADP/ATP translocase, respectively. Up-regulated gene by hypoxia was identified as Homo sapiens oscillin. Moreover, novel genes induced by hypoxia represent partial sequences of cDNAs that have not been reported or functionally identified. Up- or down-regulated expression of these genes in response to hypoxia may contribute to human hepatocarcinogenesis.