Regulation of glucose metabolism-related genes and VEGF by HIF-1alpha and HIF-1beta, but not HIF-2alpha, in gastric cancer.

Hypoxia-inducible factors (HIFs) are transcription factors that activate the transcription of target genes involved in crucial aspects of cancer development. This study investigated the expression of HIFs and their contribution to the regulation of target genes related to angiogenesis and glucose metabolism in gastric cancer. The data showed that HIFs were over-expressed in gastric cancer and that activation of the target genes was observed mainly in the early stages. Moreover, the results of the present study revealed that only HIF-1alpha, but not HIF-2alpha dimerizes with HIF-1beta and then regulates expression of target genes in response to hypoxia. The results of the present study demonstrate that HIF-1alpha and HIF-1beta enhances expression of VEGF and glucose metabolism-related genes in response to hypoxia in gastric cancer. These data offer important information regarding HIF pathways in the development of gastric cancer.