| Project/Area Number |
16591821
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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 |
Morphological basic dentistry
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| Research Institution | Niigata University |
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Principal Investigator |
CHENG Jun Niigata University, Institute of Medicine and Dentistry, Associate Professor, 医歯学系, 助教授 (40207460)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Satoshi Niigata University, Institute of Medicine and Dentistry, Assistant Professor, 医歯学系, 助手 (30397161)
SAKU Takeshi Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (40145264)
依田 浩子 新潟大学, 大学院・医歯学総合研究科, 助手 (60293213)
大城 和文 新潟大学, 大学院・医歯学総合研究科, 助手 (50332648)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | pleomorphic adenoma / salivary gland tumor / melanotic neuroectodermal tumor / karyotyping analyses / mutation of oncogene / DNA tip / DNA sequencing / capsular invasion / 唾液腺多形性腺腫 / 脈管侵襲 / 染色体転座 / 低酸素 / VEGF / 顎骨石灰化歯原性曩胞 / 細胞培養 / がん関連遺伝子 / 遺伝子変異 / RT-PCR |
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| Research Abstract |
This research project was carried out in order to study a possible molecular pathway of malignant transformation of oral benign tumors. We mainly focus on salivary pleomorphic adenoma, because we had already proposed a possibility of malignant changes of atypical tumor cells or focal carcinomas within pleomorphic adenomas. To this end, we have isolated six cell systems (designated SMAP1 to SMAP6) from a benign pleomorphic adenoma of the parotid gland of a 61 year-old female. SMAP1/3 showed duct epithelial characteristics with polygonal cell shapes, while SMAP4/6 were spindle-shaped with some myoepithelial cell differentiation. Chromosome analyses showed the cells had not only numeral abnormalities such as 5n ploidies with average numbers of 107 chromosomes but also various kinds of structural abnormalities, such as deletions, translocations, derivatives and isodicentric chromosomes. Among them, der(9)t(9; 13)(p13.3;q12.3) was shared by all of the six cell systems. In addition, they all
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had a common deletion of the last base G of codon 249 (AGG to AG_) of the p53 gene, which would result in generation of its nonsense gene product. The findings suggest that pleomorphic adenoma contains tumor cells which are precancerous and are able to transform into malignant with above mentioned gene alterations, and the present study is the first in-vitro demonstration that carcinomas can arise secondarily from adenomas in the salivary gland.
In addition to such gene alterations, there were some other biological characteristics to pleomorphic adenomas. They were capsular and vascular invasions. Their frequency was 100% (extracapular 20%) and 15%, respectively, when examined histopathologically in 104 surgical specimens. In the sites with capsular or vascular invasions, the stroma was myxoid and poorly vascularized. This histology was explained by VEGF and HIF-1a expression modes, which were hypoxia-related. In cells established from a melanotic neuroectodermal tumor of infancy, there was the same chromosome alteration found in SMAP cells, and this translocation will be worthwhile to be investigated further for the molecular mechanism of secondary malignant changes of benign tumors. Less
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