2003 Fiscal Year Final Research Report Summary
Identification of HIF-1a target genes and their biological roles in oral carcinoma.
| Project/Area Number |
14571878
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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 |
Surgical dentistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
ONO Mitsunobu Hokkaido Univ., Grad.Sch.of Dent.Med., Inst., 大学院・歯学研究科, 助手 (50281829)
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| Co-Investigator(Kenkyū-buntansha) |
HIGASHINO Fumihiro Hokkaido Univ., Grad.Sch.of Dent.Med., Inst., 大学院・歯学研究科, 助手 (50301891)
KOBAYASHI Masanobu Hokkaido Univ., Inst. Genet.Med., Asso.Prof., 遺伝子病制御研究所, 助教授 (80241321)
SHINDOH Masanobu Hokkaido Univ., Grad.Sch.of Dent.Med., Asso.Prof., 大学院・歯学研究科, 助教授 (20162802)
TOTSUKA Yasunori Hokkaido Univ., Grad.Sch.of Dent.Med., Prof., 大学院・歯学研究科, 教授 (00109456)
OHIRO Yoichi Hokkaido Univ., Med & Dent.Hospital, Inst., 医学部・歯学部附属病院, 助手 (40301915)
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| Project Period (FY) |
2002 – 2003
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| Keywords | HIF-1 / DNA microarray / metastasis |
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| Research Abstract |
Hypoxia-inducible factor 1(HIF-1) is an oxygen-regulated transcriptional activator that plays an essential role in the maintenance of oxygen homeostasis. We examined HIF-1a protein, vascularization and p53 protein in 39 biopsy specimens from tongue SCC patients HIF-1a was identified in 12 of 39 (31%) cases examined. A significant correlation was observed between HIF-1a expression and cancer cell metastasis into the cervical lymph nodes and distant organs. HIF-1a-positive tumors showed a high ratio of neovascularization with a large number and smaller diameter of blood vessels. Mutant-p53(mt-p53) expression was not significantly associated with HIF-1a expression, however, mt-p53/HIF-1a-positive cases highly correlated with metastasis, and showed significant by shorter cumulative overall survival. These results indicate that HIF-1a expression in combination with p53 status would be an indicator of neovasculanzation, which could be a new predictive and prognostic parameter for metastasis in tongue SCC.
DNA microarray analysis revealed that several candidated genes responsive for HIF-1, and pim-1 and adrenomedullin were included. pim-1 was shown to inhibit apoptosis cooperating with myc and induce tumorigenesis in blood cells. We examined pim-1 in tongue squamous cell carcinomas and pim-1 was detected in about 40% tumors Correlated expression of HIF-1a and pim-1, and the close relationship between proliferative potential and distant metastasis were identified. Adrenomedullin was identified in about 40% of oral carcinoma, and high metastatic potential with neovasculization was shown.
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