2001 Fiscal Year Final Research Report Summary
Development of gene therapy by using suppressor oncogene vHL for pancreatic cancer
| Project/Area Number |
12671132
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KOBAYASHI Masanobu Hokkaido Univ., Fac. Of Med. Prof., 遺伝子病制御研究所, 助教授 (80241321)
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| Co-Investigator(Kenkyū-buntansha) |
ONE Keisin Hokkaido Univ., Fac. Of Med., The JSPS Postdoctral Fellowship for Foreign Resercher., 遺伝子病制御研究所, 日本学術振興会外国人特別研究員
KATOH Hiroyuki Hokkaido Univ., Fac. Of Med. Prof., 大学院・医学研究科, 教授 (80002369)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Pancreatic Cancer / genetic analysis / vHL / HIF-1alpha / gene therapy |
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| Research Abstract |
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.
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