Constitutive expression of hypoxia-inducible factor-1 alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation

Hypovasculature is an outstanding characteristic of pancreatic cancers in i maging diagnosis, suggesting that blood supply is poor in pancreatic cancer tissues. Despite poor blood supply, pancreatic cancer cells survive and pr oliferate in severe hypoxia and nutrient deprivation. To demonstrate how pa ncreatic cancer cells adapt themselves to hypoxia and nutrient deprivation, we investigated the expression of hypoxia-inducible factor 1 alpha (HE-1 a lpha) protein and HIF-1-inducible genes in human pancreatic cancer cell lin es in comparison with other cancer cell lines. We found that HIF-1 alpha pr otein was constitutively expressed in 15 of 20 pancreatic cancer cell lines (75%) but in none of other cancer cell lines tested in this study. The cel ls with constitutive expression of HIF-1 alpha were more resistant to apopt osis induced by hypoxia and glucose deprivation than those without constitu tive expression of HIF-1 alpha. Transfection with HIF-1 alpha transformed t he latter cells resistant to apoptosis and increased ill vivo tumorigenicit y. Furthermore, anaerobic metabolism-associated genes, Glut1 and aldolase A , were more highly expressed in the cells with constitutive expression of H IF-1 alpha than in the cells without it. These results suggest that constit utive expression of HIF-1 alpha contributes to the survival and proliferati on of pancreatic cancer cells in hypoxia and glucose deprivation through th e activation of anaerobic metabolism.