Project/Area Number |
15592001
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pathobiological dentistry/Dental radiology
|
Research Institution | Health Scienses University of Hokkaido |
Principal Investigator |
HOSOKAWA Yoichiro Health Scienses University of Hokkaido, Dentistry, Associate Prof., 歯学部, 助教授 (70173599)
|
Co-Investigator(Kenkyū-buntansha) |
SAKAKURA Yasunori Health Scienses University of Hokkaido, Dentistry, Asociate Prof., 歯学部, 助教授 (60128915)
TSURUGA Eichi Health Scienses University of Hokkaido, Dentistry, Instractor, 歯学部, 助手 (30295901)
TANAKA Likinobu Health Scienses University of Hokkaido, Dentistry, Instractor, 歯学部, 助手 (70337038)
|
Project Period (FY) |
2003 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Keywords | hypxoia-inducible factor-lalph / apoptosis / radiation / squamous cell carcinoma / 口腔扁平上皮癌 / HIF-1α / Migration assay |
Research Abstract |
The relationship between hypoxia-inducible factor (HIF)-1alpha and radiation resistance in tumor cells has been unknown. We examined the effects of 5 Gy radiation under normoxia on the expression of HIF-1alpha, apoptosis, and migration capacity of five human oral squamous cell carcinoma (OSCC) lines. Cells in all of the lines expressed HIF-1alpha mRNA, and radiation had no influence on gene transcription. Western blot analysis did not detect the p53 tumor suppressor, which induces apoptosis through HIF-1alpha degradation, either before or after radiation exposure. Numbers of apoptotic cells increased 72 h after irradiation in lines TT, Ca9-22, and SAS, indicating low transcriptional levels of HIF- lalpha, and levels of non-cleaved caspase-3, an executioner of apoptosis, and non-cleaved poly (ADP-ribose) polymerase (PARP), a marker of DNA damage early in apoptosis, decreased at the same time. On the other hand, radiation failed to induce apoptosis or to decrease levels of non-cleaved caspase-3 and PARP in lines IS-FOM and BSC-OF, which express HIF-1alpha at high levels. Cell lines IS-FOM and BSC-OF showed high migration capacity. The other cell lines showed low capacity. These results suggest that OSCC cells expressing a high level of HIF-1alpha are resistant to radiation.
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