Development of gene therapy by using suppressor oncogene vHL for pancreatic cancer

点击翻译按钮获取中文摘要

We investigated as follows to develop gene therapy for pancreatic cancer. Two molecules, vHL and HIF-1alpha, were analyzed as the therapeutic genes. Role of vHL in pancreatic cancer was not clarified. We found that HIF-1alpha protein was constitutively expressed in 75% of pancreatic cancer cell lines but in none of other cancer cell lines. The cells with constitutive expression of HIF-1alpha were more resistant to apoptosis induced by hypoxia and glucose deprivation than those without constitutive expression of HIF-1alpha. Transfection with of HIF-1alpha transformed the latter cells resistant to apoptosis and increased in vivo tumorigenicity. Furthermore, anaerobic metabolism-associated genes, Glut1 and aldolase A, were more highly expressed in cells with constitutive expression of HIF-1alpha than in cells without it. These results suggest that constitutive expression of HIF-1alpha contributes to the survival and proliferation of ancreatic cancer cells in hypoxia and glucose deprivation through the activation of anaerobic metabolism, and HIF-1alpha could be a potential target for gene therapy against pancreatic cancer.