2012 Fiscal Year Final Research Report
Study for therapeutic strategy using the target protein expressionsystem based on protein stabilization/destabilization in the cancertracing mechanism
| Project/Area Number |
23659880
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KIYOSHIMA Tamotsu 九州大学, 大学院・歯学研究科, 准教授 (20264054)
NAGATA Kengo 九州大学, 大学院・歯学研究科, 助教 (90189134)
WADA Hiroko 九州大学, 大学院・歯学研究科, 助教 (70380706)
KOBAYASHI Ieyoshi 九州大学, 大学院・歯学研究科, 准教授 (40243951)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 腫瘍治療 / PETトレーサ / 遺伝子/蛋白調節 |
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| Research Abstract |
We studied regulations of gene/protein expression in oral squamous cell carcinoma (OSCC) cells stimulated by exogenous factors and drug-resistance of the OSCC cells in order to develop the anti-cancer therapeutic strategy using the target protein expression system based on protein stabilization/destabilization in the cancer tracing mechanism. The OSCC cells downregulated the keratinocyte differentiation-related genes and upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 and IL-6 differentially activate the STAT-signalingpathway depending on the type of OSCC. When the OSCC cells with resistance to the V-ATPase inhibitor were treated with combination with SAHA, these cells indicated the change in STAT signaling pathway and became more susceptible to the V-ATPase inhibitor. Together these findings suggest V-ATPase could be an attractive target against OSCCs. In addition, combination with other reagents such as SAHA could help V-ATPase inhibitors to induce apoptosis in the V-ATPase inhibitor-resistant OSCC cells via change in STAT-signal pathway. Together, the regulation of STAT-signaling pathway may be a pivotal target for development of the tumor specific expression system. The accumulation of these data could lead to the development of new perspectives on this disease, and potentially new therapies with few side effects, thereby improving the treatment of patients with OSCC
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