Background One effect of solid tumors is severe hypoxia of local tissues. Heme oxygenase-1 （HO-1） is highly expressed in a variety of human tumor tissues; its induction and activity are closely related to growth of ...Background One effect of solid tumors is severe hypoxia of local tissues. Heme oxygenase-1 （HO-1） is highly expressed in a variety of human tumor tissues; its induction and activity are closely related to growth of solid tumors. Hypoxia inducible factor-1 （HIF-1） is a transcription factor that regulates hypoxia signal transduction and plays a central role in tumor hypoxia regulation. However, whether and how changes in HO-1 activity affect HIF-1 gene expression has not been reported previously. Methods Hypoxia-inducible models were established using gastric cancer cell lines （SGC-7901） in a hypoxia incubator. Cells were placed in four groups： Group A, transfected by plasmid harboring HO-1 shRNA; Group B, transfected with scrambled shRNA vector; Group C, treated with hemin; and Group D, exposed to hypoxia only. Expressions of HO-1 and HIF-1 mRNAs were quantified by reverse transcription-polymerase chain reaction. Expressions of HO-1 and HIF-1 proteins were determined by immunohistochemistry and Western blotting. Results mRNA and protein levels of HO-1 and HIF-1 in the control group were significantly higher than in Group A （P 〈0.01）, but lower than in Group C （P〈0.01）. Chromatin immunoprecipitation analysis showed that HIF-1 was identified as the direct HO-1 target gene. Conclusion While affected by HIF-1, HO-1 up-regulation promotes the expression of HIF-1 and the down-regulation of HO-1 suppresses the expression of HIF-1 gene.展开更多
文摘Background One effect of solid tumors is severe hypoxia of local tissues. Heme oxygenase-1 （HO-1） is highly expressed in a variety of human tumor tissues; its induction and activity are closely related to growth of solid tumors. Hypoxia inducible factor-1 （HIF-1） is a transcription factor that regulates hypoxia signal transduction and plays a central role in tumor hypoxia regulation. However, whether and how changes in HO-1 activity affect HIF-1 gene expression has not been reported previously. Methods Hypoxia-inducible models were established using gastric cancer cell lines （SGC-7901） in a hypoxia incubator. Cells were placed in four groups： Group A, transfected by plasmid harboring HO-1 shRNA; Group B, transfected with scrambled shRNA vector; Group C, treated with hemin; and Group D, exposed to hypoxia only. Expressions of HO-1 and HIF-1 mRNAs were quantified by reverse transcription-polymerase chain reaction. Expressions of HO-1 and HIF-1 proteins were determined by immunohistochemistry and Western blotting. Results mRNA and protein levels of HO-1 and HIF-1 in the control group were significantly higher than in Group A （P 〈0.01）, but lower than in Group C （P〈0.01）. Chromatin immunoprecipitation analysis showed that HIF-1 was identified as the direct HO-1 target gene. Conclusion While affected by HIF-1, HO-1 up-regulation promotes the expression of HIF-1 and the down-regulation of HO-1 suppresses the expression of HIF-1 gene.
