Project/Area Number |
16591988
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Surgical dentistry
|
Research Institution | TOYAMA UNIVERSITY (2005) Toyama Medical and Pharmaceutical University (2004) |
Principal Investigator |
YAO Li Toyama University, Faculty of Medicine, Instructor, 医学部, 助手 (80324044)
|
Co-Investigator(Kenkyū-buntansha) |
TAKANO Yasuo Toyama University, Faculty of Medicine, Professor, 医学部, 教授 (60142022)
FURUTA Isao Toyama University, Faculty of Medicine, Professor, 医学部, 教授 (10014268)
|
Project Period (FY) |
2004 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
Keywords | Oral carcinoma / mutant α-tubulin / Cell cyclins / Cell cycle / Immunofluorescence / Flow cytometry / Immunohistochemistry / 5-FU / Cisplatin / Docetaxel / Tumor progression / Cell cycle関連蛋白 / Survivin / Ki-67 |
Research Abstract |
To investigate how expression of mutant α-tubulin involves in tumor progression in oral carcinoma, using 4 cell lines of KON,HO-1-N-1,KOSC,HSC established from oral squmous cell carcinoma (SCO) and 52 biopsy samples obtained from oral SCC, we examined the relations of mutant α-tubulin expression to cell cyclins, sensitivity of these cell lines to anticancer drugs (cisplatic,5-FU, and docetaxel), labeling indices of Ki-67 and cyclin B, apoptosis, surviving expression, and clinicopathlogical features in carcinomas. Immunofluorescent analysis showed that the level of mutant α-tubulin expression in KON and KOSC is higher than that in HO-1-N-1 and HSC and the positive rate of double staining of this protein with cyclin B is higher than that of the protein with cyclin A and D. Flow cyctometry analysis showed that KON cells positive to FITC staining also has high amount of nuclear DNA histogram. There was no obvious cytotoxic effect of 5-FU for KON and KOSC which expressed high level of mutant α-tubulin. There is a need to further examine the relationship of this protein expression with tumor resistance to anticancer drugs in vivo study. This mutant protein in carcinomas was expressed in nuclei of dysplastic epithelia and tumors, but not in normal epithelia distant to tumor. High level of this protein expression was associated with high value of labeling indices in Ki-67 and cyclin B expression, mode 3-4 of tumor invasion, and lymph node metastasis. These results suggest that expression of mutant α-tubulin in oral SCC mainly appears in G2/M phase of cell cycle and involves in tumor progression.
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