Epigenetic effect of HP1 on carcinoma cell tumorigenecity
| Project/Area Number |
15591937
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
KIYOSHIMA Tamotsu Kyushu University, Faculty of Dental Science, Research Assistant, 大学院・歯学研究院, 助手 (20264054)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Hidetaka Kyushu University, Faculty of Dental Science, Professor, 大学院・歯学研究院, 教授 (80136499)
KOBAYASHI Ieyoshi Kyushu University, Faculty of Dental Science, Associate Professor, 大学院・歯学研究院, 助教授 (40243951)
松尾 拡 九州大学, 大学院・歯学研究院, 助教授 (70238971)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | cancer / tumorigenecity / transcription / heterochromatin / epigenetics / tumor marker / 腫瘍マーカー |
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| Research Abstract |
We performed cDNA subtraction between MISK81-5 and sMISK to detect any differentially expressed genes that might be involved in the tumorigenecity of squamous cell carcinoma (SCC). These cells had been established from the same tissue of squamous cell carcinoma in our laboratory, but show their differential cellular behavior. We thus found heterochromatin protein 1 (HP1) in several genes that differentially express between them. HP1 consists of three isoforms, HP1α, HP1β and HP1γ. The HP1 mRNA expressions in five human oral SCC cell lines, three gastric adenocarcinoma cell lines and a keratinocyte cell line, were determined using semi-quantitative RT-PCR. The HP1α and HP1β expressions varied among them. Meanwhile, the HP1γ was evenly expressed. HP1-fused green fluorescent protein (GFP) showed intranuclear localization, and displayed an association with heterochromosomes in the transfected cells. Overexpression of HP1α-fused GFP decreased cellular proliferation of the transfected cells compared to the parental cells. In contrast, cells expressing mutant HP1α that had deleted the chromoshadow domain showed an increase in the proliferation. These results suggested that the amount of HPLα mRNA may influence on the tumorigenicity of squamous cell carcinoma as well as that of HP1β.
Squamous cell carcinoma antigen 1 (SCCA1) and SCCA2 were also the differentially expressing genes between MISK8l-5 and sMISK. Our examination suggested that both SCCA1 and SCCA2 play a role in the prevention of TNF-α-induced cell death by inhibiting the release of mitochondrial cytochrome c.
The S100A7 gene was one of the genes mentioned above and markedly over-expressed in SCCs in our examination as well as in the previous reports. Our transcription analysis of the S100A7 gene promoter activity suggested that the segment from -1513 to -988 contains up-regulatory elements for the transcription activity of the S100A7 gene in human oral SCC cell lines.
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Report
(4 results)
Research Products
(4 results)
